LL-37

GENEMEDICS APP

GENEMEDICS NUTRITION

Potential Benefits of LL-37
What is LL-37?
How LL-37 Works?
Chemical Structure of LL-37
Research on LL-37
Associated Side Effects of LL-37
References

Potential Benefits of LL-37

Significantly boosts immune function [1-19]
Fights inflammation [20-29]
Prevents cancer progression [30-59]
Accelerates wound healing [60-67]
Lowers the risk of heart disease [68-70]
Prevents lung injury [71-72]
Promotes bone repair [73-77]

What is LL-37?

LL-37, also known as Human Cathelicidin Antimicrobial Peptide (CAMP), is touted as a “mammal’s core tool” to fight off various harmful microorganisms in the body. It’s produced by many cell types including natural killer (NK) cells, white blood cells, and skin cells. In addition, different body systems such as the respiratory system, gastrointestinal tract, testes, and ocular surface also produce LL-37. This powerful peptide has piqued the interest of the research community because its immune-modulating activities have the potential to accelerate tissue recovery and significantly improve the survival rate of patients with chronic debilitating medical conditions.

How LL-37 Works?

The human cathelicidin LL-37 serves a critical role in the innate immune system by defending against bacterial infections. LL-37 can interact with the molecules of the cell wall and perforate cytoplasmic membranes resulting in bacterial cell death. In addition, LL-37 helps promote wound closure by stimulating the formation of new blood vessels (angiogenesis).

Chemical Structure of LL-37

Research on LL-37

Significantly Boosts Immune Function

An overwhelming body of research shows that this antimicrobial peptide regulates various important mechanisms involved in immune function:

LL-37 boosts immune function by limiting the damage caused by bacterial products and recruiting immune cells to the site of infection. [1]
A cell study found that LL-37 has the ability to inhibit the formation of bacterial biofilms (densely packed communities of microbial cells). [2]
A cell study also found that LL-37 may help enhance the immunomodulatory function of human placenta-derived MSCs (pMSCs). [3]
A study found that LL-37 was deadly against Staphylococcus aureus, the most common cause of upper respiratory tract infections. [4]
LL-37 demonstrated strong antimicrobial activity against eye pathogens (infectious microorganisms). [5]
Studies showed that LL-37 destroyed harmful microorganisms by inducing programmed cell death (apoptosis). [6-8]
A study found that LL-37 can kill a broad spectrum of bacteria. [9-10]
LL-37 boosts immune response by attracting immune cells including T cells, monocytes, neutrophils, and mast cells to the site of infection. [11-12]
LL-37 also affects the maturation of dendritic cells (antigen-presenting cells). [13]
LL-37 stimulates the production of immune cells such as cytokines, chemokines, and their receptors. [14-15]
Higher blood levels of LL-37 were associated with a lower risk of death from infection in dialysis patients. [16]
In patients with psoriasis, LL-37 worked synergistically with human beta-defensin 2 (HBD-2) in killing Staphylococcus aureus (S. aureus) bacteria. [17]
A study showed that LL-37 may be beneficial in treating patients with sepsis. [18]
A study showed that LL-37 enhanced the effects of lysozyme against S. aureus. [19]

Fights Inflammation

Aside from its immune-boosting properties, LL-37 also has potent anti-inflammatory activity according to high-quality studies:

In patients who had surgical removal of the tonsils, those with high levels of LL-37 had lesser inflammation compared to those with low LL-37. [20]
LL-37 suppresses the translocation of NF-kB to the nucleus, which creates an anti-inflammatory effect. [21]
In mice, LL-37 administration reduced the risk of inflammatory disease. [22]
LL-37 reduces inflammation by modulating inflammatory pathways in the body. [23-25]
In human gum cells, LL-37 strongly reduced the levels of pro-inflammatory cytokines and chemokines. [26]
LL-37 also modulates the inflammatory and host defense response of human white blood cells. [27]
In mouse models, LL-37 provided protection against collagen damage which normally occurs in inflammatory arthritis. [28]
A study showed that LL-37 was effective in regulating inflammation induced by interleukin-32. [29]

Prevents Cancer Progression

Studies show that LL-37 can help ward off deadly cancers:

A cell study found that LL-37 has the potential to suppress cancer growth. [30]
In another cell study, LL-37 suppressed the growth of colon cancer by inducing programmed cell death. [31]
A study found that LL-37 has an anti-cancer effect in colon cancer, gastric cancer, skin cancer, ovarian cancer, lung cancer, breast cancer, prostate cancer, hematologic malignancy, and oral cancer. [32]
In various human cancer cell lines, LL-37 exhibited anti-cancer effects similar to chemotherapeutic drugs. [33]
In human lung cancer cell lines, LL-37 suppressed cancer progression by reducing the production of pro-inflammatory cytokines. [34]
Cell studies have shown that LL-37 can inhibit the migration and invasiveness of prostate cancer cells. [35-40]
In colon cancer, gastric cancer, and skin cancer cell lines, treatment with LL-37 prevented cancer cell progression.[41-46]
In colon cancer cell lines, LL-37 destroyed cancer cells by stimulating signaling pathways involved in programmed cell death. [47-51]
In gastric cancer cell lines, LL-37 inhibited gastric cancer cell proliferation through activation of signaling pathways involved in cell cycle arrest. [52-55]
In leukemic cell lines, recombinant LL-37 treatment killed malignant cells by activating programmed cell death. [56-57]
In human oral cancer cell lines, treatment with LL-37 destroyed malignant cells by damaging their DNA. [58-59]

Accelerates Wound Healing

Studies also show that this peptide can help stimulate faster regeneration of wounds:

In patients with venous leg ulcers, LL-37 treatment was associated with a faster healing rate (almost six-fold higher) compared to placebo. [60]
In mice, LL-37 treatment promoted wound healing through the production of new blood vessels. [61]
A cell study found that LL-37 induces wound healing by stimulating the proliferation and migration of cells necessary for regeneration. [62]
In mice, LL-37 treatment improved re-epithelialization and granulation tissue formation – both of these processes are necessary for wound healing. [63-64]
Cell studies found that LL-37 improves wound healing through its antimicrobial activity. [65-66]
In patients with venous leg ulcers, low-dose LL-37 treatment markedly decreased the mean ulcer area. [67]

Lowers the Risk of Heart Disease

LL-37 has also been found to possess cardioprotective effects:

A study showed that LL-37 can protect against atherosclerosis (plaque build-up within the heart arteries). [68]
A study also found that LL-37 inhibited cell death in the heart, suggesting that increasing its level might have therapeutic benefits against heart failure. [69]
In mice, heart failure was associated with a decrease in LL-37 levels and this deficiency worsened the condition. [70]

Prevents Lung Injury

Studies found that LL-37 is essential for healthy lungs:

In mice, LL-37 attenuated the progression of lung injury by controlling inflammation and preventing infection. [71]
A study reported that LL-37 is an effective inflammatory regulator in various lung diseases. [72]

Promotes Bone Repair

Evidence also suggests that LL-37 is vital for bone repair:

A mice study found that LL-37-treated white blood cells promoted bone formation. [73]
Cell studies also found that LL-37 can help prevent bone disorders by inhibiting bone breakdown. [74-75]
In rats with bone defects, LL-37 treatment markedly induced newly formed bones. [76]
A cell study reported that LL-37 induced bone formation by recruiting stem cells into the site of injury. [77]

Associated Side Effects of LL-37

LL-37 side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on LL-37. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of LL-37. Despite this, it was listed as a side effect associated with LL-37 even though these associated side effects are very uncommon.

Side effects associated with LL-37 may include the following:

Increased inflammation
Induction of autoimmune disease
Depression
Damage to sperm surface membranes

Share This Page

Reference

Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002;169(7):3883-91.

The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses

The study by Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE, titled “The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses,” published in the Journal of Immunology in 2002, discusses the diverse roles of LL-37, a human antimicrobial peptide, in modulating innate immune responses. LL-37, part of the cathelicidin family, is known for its direct antimicrobial activity against a broad spectrum of pathogens, including bacteria, viruses, and fungi. This study extends the understanding of LL-37 by demonstrating its multifunctional role in the innate immune system beyond its antimicrobial activity.

The research highlights how LL-37 influences various aspects of the immune response, including chemotaxis (the attraction of immune cells to infection sites), modulation of inflammatory responses, and promotion of wound healing. LL-37 acts as a bridge between innate and adaptive immunity, enhancing the immune system’s ability to fight infections while also regulating inflammatory processes to prevent excessive damage to host tissues.

Full study on https://journals.aai.org/jimmunol/article/169/7/3883/35412
Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76(9):4176-82.

Human host defense peptide LL-37 prevents bacterial biofilm formation

The study by Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE, titled “Human host defense peptide LL-37 prevents bacterial biofilm formation,” published in Infection and Immunity in 2008, investigates the role of the human antimicrobial peptide LL-37 in preventing the formation of bacterial biofilms. Biofilms are complex communities of bacteria that adhere to surfaces and are encased in a protective matrix, making them significantly more resistant to antibiotics and immune system actions than free-floating bacterial cells.

The study demonstrates that LL-37, known for its broad-spectrum antimicrobial activity and modulation of immune responses, also possesses the ability to inhibit the formation of bacterial biofilms. This is a critical finding, as biofilms are implicated in a wide range of chronic infections and are notoriously difficult to eradicate with conventional antibiotic treatments.

Full study on https://journals.asm.org/doi/abs/10.1128/iai.00318-08
Oliveira-Bravo M, Sangiorgi BB, Schiavinato JL, et al. LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells. Stem Cell Res Ther. 2016;7(1):189. Published 2016 Dec 30. doi:10.1186/s13287-016-0448-3.

LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells

The study by Oliveira-Bravo M, Sangiorgi BB, Schiavinato JL, et al., titled “LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells,” published in Stem Cell Research & Therapy in December 2016, explores the interaction between the human antimicrobial peptide LL-37 and placenta-derived mesenchymal stromal cells (MSCs), focusing on the immunomodulatory effects of this interaction. MSCs are known for their potential therapeutic uses, including their ability to modulate immune responses, making them promising candidates for treating various inflammatory and autoimmune diseases.

This study demonstrates that LL-37 enhances the immunosuppressive capabilities of placenta-derived MSCs. Specifically, LL-37 treatment led to an increase in the MSCs’ ability to suppress T-cell proliferation, which is a crucial aspect of the immune response. This effect suggests that LL-37 could play a significant role in modulating the immune system by enhancing the immunosuppressive functions of MSCs, potentially leading to more effective treatments for conditions characterized by excessive or inappropriate immune responses.

Full study on https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0448-3
Aboualaiwa MH, Reznikov LR, Gansemer ND, et al. pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37. ProcNatlAcadSci USA. 2014;111(52):18703-8.

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

The study by Aboualaiwa MH, Reznikov LR, Gansemer ND, et al., titled “pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37,” published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2014, investigates how pH levels influence the antimicrobial effectiveness of β-defensin-3 and LL-37 in the airway surface liquid (ASL), which is crucial for lung health and defense against respiratory pathogens.

The ASL is a thin layer of fluid covering the airways, playing a vital role in the lung’s defense mechanism by trapping and clearing inhaled pathogens and particles. The study highlights that both β-defensin-3 and LL-37, which are key components of the innate immune system present in the ASL, exhibit their antimicrobial activities against common respiratory pathogens more effectively at certain pH levels. Importantly, it was found that their activity is enhanced in a more acidic environment, which is contrary to the neutral to slightly alkaline pH typically observed in healthy airway surface liquid.

Full study on https://www.pnas.org/doi/abs/10.1073/pnas.1422091112
Huang LC, Petkova TD, Reins RY, Proske RJ, Mcdermott AM. Multifunctional roles of human cathelicidin (LL-37) at the ocular surface. Invest Ophthalmol Vis Sci. 2006;47(6):2369-80.

Multifunctional roles of human cathelicidin (LL-37) at the ocular surface

The study by Huang LC, Petkova TD, Reins RY, Proske RJ, McDermott AM, titled “Multifunctional roles of human cathelicidin (LL-37) at the ocular surface,” published in Investigative Ophthalmology & Visual Science in 2006, explores the diverse functions of the antimicrobial peptide LL-37 at the ocular surface. LL-37, a member of the cathelicidin family, is known for its broad-spectrum antimicrobial activity and its role in modulating immune responses. This study extends our understanding of LL-37 by highlighting its multifaceted roles in eye health and disease.

The research demonstrates that LL-37 is not only involved in providing antimicrobial protection against various pathogens at the ocular surface but also plays a significant role in wound healing, inflammation modulation, and potentially in protecting against ocular surface diseases. The study found that LL-37 can stimulate epithelial cell migration, which is crucial for wound healing, and can modulate the inflammatory response, reducing the risk of excessive inflammation that can lead to tissue damage.

Full study on https://iovs.arvojournals.org/article.aspx?articleid=2126385
De yang, Chen Q, Schmidt AP, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000;192(7):1069-74.

LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells

The study by De Yang, Chen Q, Schmidt AP, et al., titled “LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells,” published in the Journal of Experimental Medicine in 2000, focuses on the chemotactic properties of LL-37 and its interaction with the formyl peptide receptor-like 1 (FPRL1) on immune cells.

LL-37, a human cathelicidin antimicrobial peptide, is known for its broad-spectrum antimicrobial activity. This study expands its known functions by demonstrating LL-37’s role in immune regulation, specifically its ability to attract (chemoattract) various types of immune cells, including neutrophils, monocytes, and T cells, to sites of infection or inflammation. The study identifies FPRL1, a G protein-coupled receptor (GPCR), as the receptor through which LL-37 mediates this chemotactic activity.

Full study on https://rupress.org/jem/article-abstract/192/7/1069/8245
Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003;55(1):27-55.

Mechanisms of antimicrobial peptide action and resistance

The review article by Yeaman MR, Yount NY, titled “Mechanisms of antimicrobial peptide action and resistance,” published in Pharmacological Reviews in 2003, provides a comprehensive overview of the actions of antimicrobial peptides (AMPs) and the mechanisms by which microbes develop resistance against them. AMPs are a diverse group of molecules that play a crucial role in the innate immune system across a wide range of organisms, providing a first line of defense against microbial pathogens.

The article discusses the various mechanisms through which AMPs exert their antimicrobial effects. These mechanisms include disrupting microbial membrane integrity, interfering with intracellular targets, and modulating the host immune response. The review highlights that AMPs target microbial cells through mechanisms that are distinct from those of conventional antibiotics, which often target specific biochemical pathways. This broad mode of action reduces the likelihood of resistance development but does not eliminate it.

Full study on https://pharmrev.aspetjournals.org/content/55/1/27.short
Cassagnes LE, Hervé V, Nepveu F, Hureau C, Faller P, Collin F. The catalytically active copper-amyloid-Beta state: coordination site responsible for reactive oxygen species production. AngewChemInt Ed Engl. 2013;52(42):11110-3.

The catalytically active copper‐amyloid‐beta state: coordination site responsible for reactive oxygen species production

The study by Cassagnes LE, Hervé V, Nepveu F, Hureau C, Faller P, Collin F, titled “The catalytically active copper-amyloid-Beta state: coordination site responsible for reactive oxygen species production,” published in Angewandte Chemie International Edition in 2013, focuses on the interaction between copper ions and amyloid-beta (Aβ) peptides, which are critically involved in Alzheimer’s disease (AD) pathology. The study aims to elucidate the molecular mechanisms underlying the generation of reactive oxygen species (ROS) in the presence of copper-bound Aβ peptides, a process that contributes to oxidative stress and neuronal damage in AD.

Amyloid-beta peptides can bind metal ions, including copper, leading to the formation of a complex that has been shown to catalyze the production of ROS. These highly reactive molecules can damage cellular components, contributing to the neurodegeneration observed in Alzheimer’s disease. Understanding the specific coordination site of copper in the Aβ peptide that is responsible for ROS production is crucial for elucidating the role of metal ions in AD pathology and for developing potential therapeutic strategies targeting metal-peptide interactions.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/ange.201305372
Dürr UHN, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. BiochimBiophysActa. 2006 Sep;1758:1408–1425.

LL-37, the only human member of the cathelicidin family of antimicrobial peptides

The review article by Dürr UHN, Sudheendra US, Ramamoorthy A, titled “LL-37, the only human member of the cathelicidin family of antimicrobial peptides,” published in Biochimica et Biophysica Acta (BBA) – Biomembranes in September 2006, provides an extensive overview of LL-37, the sole human cathelicidin antimicrobial peptide. Cathelicidins are a family of peptides known for their broad-spectrum antimicrobial activities and are found in various species. LL-37 plays a crucial role in the human innate immune system, providing a first line of defense against a wide range of pathogens, including bacteria, viruses, fungi, and parasites.

The article discusses the structure, mechanism of action, and the diverse biological functions of LL-37 beyond its antimicrobial activity. LL-37 is produced as a precursor protein, hCAP-18, which is cleaved to release the active LL-37 peptide. This peptide is unique in its ability to interact with microbial membranes, leading to membrane disruption and pathogen death. Moreover, LL-37 is involved in modulating the immune response, including inducing chemokine production, influencing cell proliferation and migration, and playing roles in wound healing and inflammation regulation.

Full study on https://www.sciencedirect.com/science/article/pii/S000527360600126X
Duplantier AJ, van Hoek ML. The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds. Front Immunol. 2013;4:143.

The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds

The article by Duplantier AJ, van Hoek ML, titled “The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds,” published in Frontiers in Immunology in 2013, discusses the therapeutic potential of LL-37, the only human cathelicidin antimicrobial peptide, in treating wounds infected with multiple types of pathogens. Polymicrobial infections, which involve more than one microbial species, are particularly challenging to treat due to the complex interactions between different pathogens and the host’s immune response. Such infections are common in chronic wounds, including diabetic ulcers, venous leg ulcers, and pressure ulcers, and they significantly hinder the healing process.

The review highlights LL-37’s broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites, making it a promising agent for treating polymicrobial wound infections. LL-37 not only directly kills pathogens but also modulates the immune response to promote healing. It can enhance the recruitment of immune cells to the site of infection, stimulate angiogenesis (the formation of new blood vessels), and promote re-epithelialization (the restoration of the epidermis).

Full study on https://www.frontiersin.org/articles/10.3389/fimmu.2013.00143/full
De Yang, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000 Oct 2;192:1069–1074

LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells

The study by De Yang, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al., titled “LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells,” was published in the Journal of Experimental Medicine on October 2, 2000. This research investigates the role of LL-37, a human cathelicidin antimicrobial peptide, in chemotaxis, specifically its ability to attract various immune cells from peripheral blood.

LL-37 is known for its antimicrobial properties, but this study delves into its additional function as a chemoattractant for immune cells. The research demonstrates that LL-37 has the capacity to chemoattract peripheral blood neutrophils, monocytes, and T cells, which are essential components of the immune system involved in defense against infections and immune responses.

Full study on https://rupress.org/jem/article-abstract/192/7/1069/8245
Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology. 2002 May;106:20–26.

A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis

The study by Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, et al., titled “A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis,” was published in Immunology in May 2002. This research investigates the effects of LL-37, a member of the cathelicidin family of human antibacterial peptides, on mast cells, which are immune cells involved in inflammatory and allergic responses.

The study reveals that LL-37 has the capacity to induce chemotaxis, the directed migration of cells, in mast cells. Chemotaxis is an essential process in the immune response, as it allows immune cells to move toward sites of infection or inflammation. LL-37’s ability to attract mast cells suggests its involvement in regulating immune responses, particularly those associated with inflammation and allergy.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2567.2002.01398.x
Davidson DJ, Currie AJ, Reid GSD, Bowdish DME, MacDonald KL, Ma RC, et al. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J ImmunolBaltimMd 1950. 2004 Jan 15;172:1146–1156.

The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization

The study by Davidson DJ, Currie AJ, Reid GSD, Bowdish DME, MacDonald KL, Ma RC, et al., titled “The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization,” was published in the Journal of Immunology (Baltimore, Md. : 1950) on January 15, 2004. This research investigates the impact of LL-37, a cationic antimicrobial peptide, on the differentiation of dendritic cells and the subsequent polarization of T cells.

Dendritic cells are critical antigen-presenting cells that play a central role in initiating and shaping immune responses. This study demonstrates that LL-37 has a significant influence on dendritic cell differentiation, leading to the development of dendritic cells with altered characteristics. LL-37-treated dendritic cells exhibit changes in surface markers and cytokine production, suggesting a modification in their maturation and function.

Full study on https://journals.aai.org/jimmunol/article/172/2/1146/71732
Pistolic J, Cosseau C, Li Y, Yu JJ, Filewod NCJ, Gellatly S, et al. Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway. J Innate Immun. 2009;1:254–267.

Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-κB signaling pathway

The study by Pistolic J, Cosseau C, Li Y, Yu JJ, Filewod NCJ, Gellatly S, et al., titled “Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway,” was published in the Journal of Innate Immunity in 2009. This research investigates the interaction between LL-37, a host defense peptide, and human bronchial epithelial cells, with a focus on its effect on the expression of interleukin-6 (IL-6) and the involvement of the NF-kappaB signaling pathway.

The study demonstrates that LL-37 has the capacity to induce the expression of IL-6 in human bronchial epithelial cells. IL-6 is a pro-inflammatory cytokine that plays a crucial role in the immune response, particularly in inflammation and infection. LL-37’s ability to stimulate IL-6 production suggests its role in initiating and amplifying the local immune response in the respiratory tract.

Full study on https://karger.com/jin/article-abstract/1/3/254/179822
Montreekachon P, Chotjumlong P, Bolscher JGM, Nazmi K, Reutrakul V, Krisanaprakornkit S. Involvement of P2X(7) purinergic receptor and MEK1/2 in interleukin-8 up-regulation by LL-37 in human gingival fibroblasts. J Periodontal Res. 2011 Jun;46:327–337.

Involvement of P2X(7) purinergic receptor and MEK1/2 in interleukin-8 up-regulation by LL-37 in human gingival fibroblasts

The study by Montreekachon P, Chotjumlong P, Bolscher JGM, Nazmi K, Reutrakul V, Krisanaprakornkit S, titled “Involvement of P2X(7) purinergic receptor and MEK1/2 in interleukin-8 up-regulation by LL-37 in human gingival fibroblasts,” was published in the Journal of Periodontal Research in June 2011. This research investigates the mechanisms through which LL-37, a host defense peptide, up-regulates interleukin-8 (IL-8) in human gingival fibroblasts, focusing on the involvement of the P2X(7) purinergic receptor and the MEK1/2 signaling pathway.

The study reveals that LL-37 has the ability to up-regulate the expression of IL-8, a pro-inflammatory chemokine, in human gingival fibroblasts. IL-8 plays a crucial role in recruiting immune cells to sites of inflammation, and its up-regulation suggests LL-37’s involvement in the local immune response within gingival tissues.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0765.2011.01346.x
Gombart AF, Bhan I, Borregaard N, et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009;48(4):418-24

Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis

The study by Gombart AF, Bhan I, Borregaard N, et al., titled “Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis,” was published in Clinical Infectious Diseases in 2009. This research investigates the relationship between the plasma levels of cathelicidin antimicrobial peptide (hCAP18) and infectious disease mortality in patients undergoing hemodialysis.

Hemodialysis is a medical procedure used to treat patients with kidney failure, and these patients are known to have an increased susceptibility to infections. Cathelicidin antimicrobial peptide (hCAP18) is a host defense peptide with antimicrobial properties, and it plays a crucial role in the innate immune system’s defense against infections.

The study reveals that patients undergoing hemodialysis with low plasma levels of hCAP18 are at a higher risk of infectious disease-related mortality. In other words, individuals with lower levels of this antimicrobial peptide are more vulnerable to severe infections and have a higher likelihood of succumbing to infectious diseases.

Full study on https://academic.oup.com/cid/article-abstract/48/4/418/283660
Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002 Oct 10;347(15):1151-60. doi: 10.1056/NEJMoa021481. PMID: 12374875.

Endogenous antimicrobial peptides and skin infections in atopic dermatitis

The study by Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY, titled “Endogenous antimicrobial peptides and skin infections in atopic dermatitis,” was published in the New England Journal of Medicine on October 10, 2002. This research explores the role of endogenous antimicrobial peptides in the context of skin infections in individuals with atopic dermatitis, a chronic inflammatory skin condition.

Atopic dermatitis is known for its association with recurrent skin infections, and this study investigates the mechanisms underlying the susceptibility of individuals with atopic dermatitis to skin infections. One aspect of the study focuses on endogenous antimicrobial peptides, which are naturally occurring molecules that play a crucial role in the skin’s defense against infections.

Full study on https://www.nejm.org/doi/full/10.1056/NEJMoa021481
Ciornei CD, Sigurdardóttir T, Schmidtchen A, Bodelsson M. Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37. Antimicrob Agents Chemother. 2005 Jul;49(7):2845-50. doi: 10.1128/AAC.49.7.2845-2850.2005. PMID: 15980359; PMCID: PMC1168709.

Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37

The study by Ciornei CD, Sigurdardóttir T, Schmidtchen A, Bodelsson M, titled “Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37,” was published in Antimicrobial Agents and Chemotherapy in July 2005. This research explores various properties and activities of analogs of the human cathelicidin LL-37, including their antimicrobial activity, chemoattractant activity, lipopolysaccharide (LPS) neutralization, cytotoxicity, and susceptibility to inhibition by serum.

Cathelicidin LL-37 is an antimicrobial peptide known for its role in host defense against infections. The study investigates analogs of LL-37, which are similar molecules with potential therapeutic applications.

Full study on https://journals.asm.org/doi/abs/10.1128/AAC.49.7.2845-2850.2005
Chen X, Niyonsaba F, Ushio H, Okuda D, Nagaoka I, Ikeda S, Okumura K, Ogawa H. Synergistic effect of antibacterial agents human beta-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli. J Dermatol Sci. 2005 Nov;40(2):123-32. doi: 10.1016/j.jdermsci.2005.03.014. Epub 2005 Jun 15. PMID: 15963694.

Synergistic effect of antibacterial agents human β-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

In a study published in the Journal of Dermatological Science in November 2005, researchers investigated the synergistic effects of natural antibacterial agents, including human beta-defensins, cathelicidin LL-37, and lysozyme, against common bacterial pathogens Staphylococcus aureus and Escherichia coli. Their findings revealed that the combination of these antibacterial agents had a synergistic effect, resulting in enhanced antibacterial activity against both pathogens compared to individual agents. This research sheds light on the intricate mechanisms employed by the innate immune system to combat bacterial infections and suggests potential applications for developing more effective antibacterial treatments by harnessing the synergy between these natural antimicrobial molecules.

Full study on https://www.sciencedirect.com/science/article/pii/S0923181105001374
Elenius V, Palomares O, Waris M, et al. The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response. PLoS ONE. 2017;12(2):e0172350.

The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

In a study published in PLOS ONE in 2017, researchers investigated the interplay between serum levels of vitamins A, D, E, and the antimicrobial peptide LL-37 in relation to allergic status, tonsillar virus detection, and immune responses. This comprehensive analysis aimed to uncover associations between these serum components and various aspects of the immune system. The findings provided insights into the potential roles of these nutrients and LL-37 in influencing immune function, allergic conditions, and the presence of viral infections in the tonsils, contributing to our understanding of their relevance in immune responses and health outcomes.

Full study on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172350
Mookherjee, N. et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 176, 2455–2464 (2006).

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37

In a study published in the Journal of Immunology in 2006, Mookherjee and colleagues investigate the impact of the endogenous human host defense peptide LL-37 on the Toll-like receptor (TLR)-mediated inflammatory response, a critical component of the innate immune system’s defense against pathogens. LL-37, known for its antimicrobial properties, is revealed to have a regulatory role in modulating the inflammatory response triggered by TLR activation. Depending on the specific TLRs involved and the context of the immune response, LL-37 can either enhance or suppress the production of inflammatory cytokines. These findings illuminate LL-37’s multifaceted role in immune regulation, providing insights into its potential applications for modulating immune responses to microbial challenges and contributing to our understanding of innate immune system dynamics.

Full study on https://journals.aai.org/jimmunol/article/176/4/2455/73544
Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota. Sun J, Furio L, Mecheri R, van der Does AM, Lundeberg E, Saveanu L, Chen Y, van Endert P, Agerberth B, Diana J. Immunity. 2015 Aug 18;43(2):304-17.

Pancreatic β-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota

In a study published in Immunity in 2015, Sun et al. investigate the pivotal role of pancreatic β-cells and an immunoregulatory antimicrobial peptide influenced by the gut microbiota in restraining autoimmune diabetes. Focusing on the autoimmune attack on pancreatic β-cells seen in conditions like type 1 diabetes, the research unveils the expression of an immunoregulatory antimicrobial peptide that appears to play a critical role in immune regulation. Notably, the study highlights the influence of the gut microbiota on the production of this peptide, suggesting a complex interplay between pancreatic β-cells, gut microorganisms, and immune modulation. These findings contribute to our understanding of the mechanisms underlying autoimmune diabetes and offer potential insights into therapeutic strategies for its management.

Full study on https://www.cell.com/immunity/pdf/S1074-7613(15)00302-7.pdf
Kahlenberg JM, Kaplan MJ. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol. 2013;191(10):4895-901.

Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease

In their 2013 review published in the Journal of Immunology, Kahlenberg and Kaplan examine the pivotal role of the antimicrobial peptide LL-37 in inflammation and autoimmune diseases. LL-37, produced by various cell types, emerges as a multifaceted player in immune regulation. The review explores LL-37’s dual nature, capable of both promoting and dampening inflammatory responses, depending on the context. Moreover, it delves into LL-37’s involvement in autoimmune diseases like systemic lupus erythematosus (SLE) and psoriasis, shedding light on its contributions to disease pathogenesis. This comprehensive overview underscores LL-37’s intricate interactions within the immune system and highlights its potential as a target for innovative therapeutic strategies in autoimmune and inflammatory disorders.

Full study on https://journals.aai.org/jimmunol/article/191/10/4895/86783
Yu X, Quan J, Long W, et al. LL-37 inhibits LPS-induced inflammation and stimulates the osteogenic differentiation of BMSCs via P2X7 receptor and MAPK signaling pathway. Exp Cell Res. 2018;372(2):178-187.

LL-37 inhibits LPS-induced inflammation and stimulates the osteogenic differentiation of BMSCs via P2X7 receptor and MAPK signaling pathway

In a study published in Experimental Cell Research in 2018, Yu et al. investigate the versatile role of the antimicrobial peptide LL-37. They find that LL-37 demonstrates dual functionality by inhibiting lipopolysaccharide (LPS)-induced inflammation and promoting the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). The study reveals that LL-37 exerts its anti-inflammatory effects through the P2X7 receptor, a cell membrane receptor, and engages the MAPK signaling pathway, a crucial intracellular signaling pathway. This research sheds light on LL-37’s potential as a therapeutic agent in conditions involving inflammation and bone health, offering insights into its mechanisms of action and signaling pathways involved.

Full study on https://www.sciencedirect.com/science/article/pii/S001448271830572X
Tjabringa GS, Rabe KF, Hiemstra PS. The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung. PulmPharmacolTher. 2005;18(5):321-7.

The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung

In their 2005 review published in Pulmonary Pharmacology & Therapeutics, Tjabringa, Rabe, and Hiemstra provide a comprehensive exploration of the multifunctional role of the human cathelicidin LL-37 in infection and inflammation within the lung. Focusing on this versatile antimicrobial peptide, the review underscores LL-37’s significance in combating lung infections by targeting and neutralizing pathogens. Furthermore, it illuminates LL-37’s capacity for immunomodulation, shaping inflammatory responses in the lung. The article also delves into LL-37’s relevance in lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis, where inflammation and infections are prominent features. By elucidating the therapeutic potential of LL-37 and related peptides in managing lung infections and inflammation, this review contributes to a deeper understanding of LL-37’s multifaceted roles in maintaining respiratory health.

Full study on https://www.sciencedirect.com/science/article/pii/S1094553905000155
Jönsson D, Nilsson BO. The antimicrobial peptide LL-37 is anti-inflammatory and proapoptotic in human periodontal ligament cells. J Periodont Res. 2012;47(3):330-5.

The antimicrobial peptide LL-37 is anti-inflammatory and proapoptotic in human periodontal ligament cells

In their 2012 study published in the Journal of Periodontal Research, Jönsson and Nilsson investigate the impact of the antimicrobial peptide LL-37 on human periodontal ligament cells, a critical component of the structures supporting teeth. The research uncovers that LL-37 possesses dual functionality, demonstrating anti-inflammatory properties by attenuating inflammatory responses within periodontal ligament cells. Additionally, LL-37 exhibits proapoptotic effects, suggesting its potential involvement in programmed cell death, which can be significant for tissue homeostasis and repair. These findings contribute to a deeper understanding of LL-37’s role in modulating inflammation and apoptosis within periodontal tissues, offering insights into its implications for periodontal health.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0765.2011.01436.x
Alalwani SM, Sierigk J, Herr C, et al. The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol. 2010;40(4):1118–1126. doi:10.1002/eji.200939275.

The antimicrobial peptide LL‐37 modulates the inflammatory and host defense response of human neutrophils

In their 2010 study published in the European Journal of Immunology, Alalwani et al. delve into the multifaceted effects of the antimicrobial peptide LL-37 on human neutrophils, pivotal immune cells crucial for defending against infections. The research uncovers that LL-37 plays a dynamic role in modulating inflammatory responses within neutrophils, capable of both enhancing and suppressing inflammatory signaling pathways, contingent on the specific context. Moreover, LL-37 emerges as a promoter of host defense mechanisms within neutrophils, enhancing their abilities in processes such as phagocytosis and microbial killing. These findings shed light on LL-37’s intricate involvement in the immune system, illuminating its potential as a therapeutic agent in infectious and inflammatory conditions.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.200939275
Chow LN, Choi KY, Piyadasa H, Bossert M, Uzonna J, Klonisch T, Mookherjee N. Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis. Mol Immunol. 2014 Feb;57(2):86-92. doi: 10.1016/j.molimm.2013.08.011. Epub 2013 Oct 1. PMID: 24091294.

Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis

In their 2014 study published in Molecular Immunology, Chow et al. investigate the therapeutic potential of the human cathelicidin LL-37-derived peptide IG-19 in a murine model of collagen-induced arthritis, a representative model for rheumatoid arthritis. Focusing on IG-19, a peptide derived from the immune-modulating antimicrobial peptide LL-37, the research unveils that IG-19 exerts protective effects in this arthritis model by ameliorating disease severity. These findings highlight IG-19’s promising role as a therapeutic agent for rheumatoid arthritis and autoimmune disorders, shedding light on its immunomodulatory properties that contribute to its beneficial impact.

Full study on https://www.sciencedirect.com/science/article/pii/S0161589013004938
Choi KY, Napper S, Mookherjee N. Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced inflammation. Immunology. 2014 Sep;143(1):68-80. doi: 10.1111/imm.12291. PMID: 24666281; PMCID: PMC4137957.

Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced inflammation

In their 2014 study published in Immunology, Choi et al. investigate the regulatory effects of the human cathelicidin LL-37 and its derivative IG-19 on interleukin-32-induced inflammation. Interleukin-32 (IL-32) is known to play a role in promoting inflammatory responses. The research reveals that LL-37 and IG-19 exert anti-inflammatory actions by inhibiting IL-32-induced inflammation. These peptides effectively suppress IL-32-induced cytokine production and immune cell activation. This study provides valuable insights into the immunomodulatory properties of LL-37 and its derivative IG-19, suggesting their potential as therapeutic agents for conditions involving excessive inflammation.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1111/imm.12291
Hayashi M, Kuroda K, Ihara K, Iwaya T, Isogai E. Suppressive effect of an analog of the antimicrobial peptide of LL‑37 on colon cancer cells via exosome‑encapsulated miRNAs. Int J Mol Med. 2018;42(6):3009-3016.

Suppressive effect of an analog of the antimicrobial peptide of LL‑37 on colon cancer cells via exosome‑encapsulated miRNAs

In their 2018 study published in the International Journal of Molecular Medicine, Hayashi et al. investigate the potential anti-cancer properties of an analog of the antimicrobial peptide LL-37 in the context of colon cancer cells. This research reveals that the LL-37 analog exerts suppressive effects on colon cancer cell growth and proliferation. Furthermore, the study uncovers a novel mechanism involving exosomes, small vesicles released by cells, and their encapsulated miRNAs, which mediate the anticancer actions of the LL-37 analog. These findings offer insights into the potential therapeutic applications of LL-37 analogs in combatting colon cancer and shed light on the role of exosome-mediated mechanisms in regulating cancer cell behavior.

Full study on https://www.spandidos-publications.com/ijmm/42/6/3009
Ren SX, Cheng AS, To KF, et al. Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Res. 2012;72(24):6512-23.

Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer

In their 2012 study published in Cancer Research, Ren et al. investigate the role of the host immune defense peptide LL-37 in combatting colon cancer. This research uncovers that LL-37 possesses notable anticancer properties by inducing apoptosis, a form of cell death, in colon cancer cells through a caspase-independent mechanism. These findings highlight LL-37’s potential as a promising agent for suppressing colon cancer growth and offer insights into novel pathways for apoptosis induction in cancer cells, providing valuable contributions to cancer therapeutics.

Full study on https://aacrjournals.org/cancerres/article-abstract/72/24/6512/576212
Chen X, Zou X, Qi G, et al. Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer. Cell PhysiolBiochem. 2018;47(3):1060-1073.

Roles and mechanisms of human cathelicidin LL-37 in cancer

In their 2018 study published in Cell Physiology and Biochemistry, Chen et al. conduct a comprehensive investigation into the diverse roles and underlying mechanisms of the human cathelicidin LL-37 in the context of cancer. The research explores LL-37’s multifaceted impact on cancer, including its effects on cancer cell growth, proliferation, apoptosis, and metastasis. Moreover, the study highlights LL-37’s immunomodulatory properties within the tumor microenvironment, shedding light on its influence on the interplay between cancer cells and immune cells. This research suggests that LL-37 may hold promise as a potential therapeutic target in cancer treatment and underscores its significance in the broader landscape of cancer biology and therapy.

Full study on https://karger.com/cpb/article/47/3/1060/75103
Kuroda K, Okumura K, Isogai H, Isogai E. The Human Cathelicidin Antimicrobial Peptide LL-37 and Mimics are Potential Anticancer Drugs. Front Oncol. 2015;5:144.

The human cathelicidin antimicrobial peptide LL-37 and mimics are potential anticancer drugs

In their 2015 study published in Frontiers in Oncology, Kuroda et al. investigate the potential of the human cathelicidin antimicrobial peptide LL-37 and LL-37 mimics as candidates for anticancer drugs. This research delves into the role of LL-37 in cancer therapy, highlighting its capacity to inhibit cancer cell growth and induce apoptosis. Additionally, the study explores LL-37 mimics, synthetic compounds designed to replicate LL-37’s properties, as promising agents for cancer treatment. The findings suggest that LL-37 and its mimics hold significant potential as novel anticancer drugs, offering a new avenue for cancer therapy development and emphasizing their relevance in oncology research.

Full study on https://www.frontiersin.org/articles/10.3389/fonc.2015.00144/full
Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sørensen OE, Borregaard N, Rabe KF, Hiemstra PS: The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003; 171: 6690-6696.

The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor

In their 2003 study published in the Journal of Immunology, Tjabringa et al. investigate the role of the antimicrobial peptide LL-37 in activating innate immunity at the airway epithelial surface. The research reveals that LL-37 achieves this by transactivating the epidermal growth factor receptor (EGFR), a key molecular signaling pathway. This transactivation of EGFR leads to the initiation of innate immune responses in the airway epithelium, contributing to the host’s defense against infections and highlighting LL-37’s multifunctional properties in immune regulation and host defense.

Full study on https://journals.aai.org/jimmunol/article/171/12/6690/72072
Piktel E, Niemirowicz K, Wnorowska U, Wątek M, Wollny T, Głuszek K, Góźdź S, Levental I, Bucki R: The role of cathelicidin LL-37 in cancer development. Arch ImmunolTherExp (Warsz) 2016; 64: 33-46.

The role of cathelicidin LL-37 in cancer development

In their 2016 review published in the Archives of Immunology and Experimental Therapy, Piktel et al. explore the role of the cathelicidin LL-37 in cancer development. The review provides an overview of LL-37’s multifaceted functions, including its antimicrobial properties and involvement in immune responses. It also delves into LL-37’s potential impact on cancer development and progression. The authors discuss how LL-37 may influence various aspects of cancer biology, such as tumor cell proliferation, angiogenesis, and metastasis, and its potential as a target for cancer therapy. This comprehensive review sheds light on the complex relationship between LL-37 and cancer and highlights the need for further research to elucidate its precise role in cancer development.

Full study on https://link.springer.com/article/10.1007/s00005-015-0359-5
Choi KY, Napper S, Mookherjee N: Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced inflammation. Immunology 2014; 143: 68-80.

Human cathelicidin LL‐37 and its derivative IG‐19 regulate interleukin‐32‐induced inflammation

In their 2014 study published in Immunology, Choi et al. investigate the regulatory role of the human cathelicidin LL-37 and its derivative IG-19 in interleukin-32-induced inflammation. The research explores how LL-37 and IG-19 modulate the inflammatory responses triggered by interleukin-32. The study reveals that both LL-37 and IG-19 have the capacity to regulate and dampen interleukin-32-induced inflammation, highlighting their potential as anti-inflammatory agents. This research contributes to a better understanding of the intricate mechanisms involved in immune regulation and inflammation control, particularly in the context of interleukin-32-mediated responses.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1111/imm.12291
Di Virgilio F, Falzoni S, Giuliani AL, Adinolfi E: P2 receptors in cancer progression and metastatic spreading. CurrOpinPharmacol 2016; 29: 17-25.

P2 receptors in cancer progression and metastatic spreading

In their 2016 review published in Current Opinion in Pharmacology, Di Virgilio et al. provide insights into the role of P2 receptors in cancer progression and metastatic spreading. The review explores the significance of P2 receptors in the context of cancer biology and how they contribute to the various stages of cancer development, including tumor growth, invasion, and metastasis. The authors discuss the potential of P2 receptors as therapeutic targets in cancer treatment and shed light on the complex interplay between purinergic signaling and cancer progression. This review offers valuable perspectives on the role of P2 receptors in cancer and their potential implications for the development of novel anticancer strategies.

Full study on https://www.sciencedirect.com/science/article/pii/S1471489216300455
Qiu Y, Li WH, Zhang HQ, Liu Y, Tian XX, Fang WG: P2X7 mediates ATP-driven invasiveness in prostate cancer cells. PLoS One 2014; 9:e114371.

P2X7 mediates ATP-driven invasiveness in prostate cancer cells

In their 2014 study published in PLoS One, Qiu et al. investigate the role of the P2X7 receptor in mediating ATP-driven invasiveness in prostate cancer cells. The research focuses on how ATP, acting through the P2X7 receptor, influences the invasiveness of prostate cancer cells. The study reveals that activation of P2X7 by ATP promotes the invasiveness of these cancer cells, suggesting a potential mechanism by which purinergic signaling contributes to cancer progression and metastasis in the context of prostate cancer. This study provides insights into the molecular pathways involved in cancer cell invasiveness and highlights the importance of P2X7 as a potential therapeutic target in prostate cancer research and treatment.

Full study on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114371
Cha HR, Lee JH, Hensel JA, Sawant AB, Davis BH, Lee CM, Deshane JS, Ponnazhagan S: Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. Prostate 2016; 76: 624-636.

Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages

In their 2016 study published in Prostate, Cha et al. investigate the role of a prostate cancer-derived cathelicidin-related antimicrobial peptide (CRAMP) in promoting macrophage differentiation and polarization of immature myeloid progenitors towards protumorigenic macrophages. The research explores how this CRAMP, produced by prostate cancer cells, contributes to shaping the tumor microenvironment. The study reveals that CRAMP facilitates the differentiation of immature myeloid progenitors into tumor-promoting macrophages, suggesting a mechanism by which prostate cancer cells can manipulate the immune response in their favor. These findings provide insights into the complex interactions within the tumor microenvironment and highlight the potential impact of CRAMP on immune cell polarization in the context of prostate cancer.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/pros.23155
Roger S, Jelassi B, Couillin I, Pelegrin P, Besson P, Jiang LH: Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives. BiochimBiophysActa 2015; 1848: 2584-2602.

Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives

In their 2015 review published in Biochimica et Biophysica Acta, Roger et al. provide a comprehensive overview of the roles of the P2X7 receptor in solid tumor progression and discuss potential therapeutic perspectives. The review delves into the multifaceted functions of the P2X7 receptor in the context of various solid tumors, including its involvement in cancer cell proliferation, migration, angiogenesis, and immune evasion. The authors also explore the potential therapeutic strategies targeting the P2X7 receptor as a means to impede cancer progression. This review offers valuable insights into the complex relationship between purinergic signaling via the P2X7 receptor and solid tumor development, highlighting its significance in cancer research and therapy.

Full study on https://www.sciencedirect.com/science/article/pii/S0005273614003642
Piktel E, Niemirowicz K, Wnorowska U, Wątek M, Wollny T, Głuszek K, Góźdź S, Levental I, Bucki R: The role of cathelicidin LL-37 in cancer development. Arch ImmunolTherExp (Warsz) 2016; 64: 33-46.

The role of cathelicidin LL-37 in cancer development

In their 2016 study published in Archives of Immunology and Experimental Therapy, Piktel et al. investigate the role of the cathelicidin LL-37 in cancer development. This comprehensive review explores the multifaceted functions of LL-37, including its antimicrobial properties and its potential impact on cancer biology. The authors discuss the intricate relationship between LL-37 and various aspects of cancer, such as tumor cell proliferation, angiogenesis, and metastasis. Additionally, the review highlights the immunomodulatory properties of LL-37 within the tumor microenvironment and its potential implications for cancer progression. This study provides valuable insights into the complex interplay between LL-37 and cancer development, emphasizing the need for further research to elucidate its precise role in oncology.

Full study on https://link.springer.com/article/10.1007/s00005-015-0359-5
Tuomela JM, Sandholm JA, Kaakinen M, Hayden KL, Haapasaari KM, Jukkola-Vuorinen A, Kauppila JH, Lehenkari PP, Harris KW, Graves DE, Selander KS: Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro. Breast Cancer Res Treat 2016; 155: 261-271.

Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro

In their 2016 study published in Breast Cancer Research and Treatment, Tuomela et al. investigate the impact of telomeric G-quadruplex-forming DNA fragments on breast cancer cells. The research focuses on how these DNA fragments induce invasion in breast cancer cells in vitro, particularly through Toll-like receptor 9 (TLR9)-mediated mechanisms. The study also explores the regulatory role of LL-37, a cathelicidin peptide, in this process. The findings suggest that telomeric DNA fragments can promote invasion in breast cancer cells, and LL-37 plays a role in regulating this invasive behavior. This research contributes to our understanding of the complex interactions between DNA fragments, innate immune receptors, and LL-37 in the context of breast cancer cell invasion.

Full study on https://link.springer.com/article/10.1007/s10549-016-3683-5
Wu WK, Wang G, Coffelt SB, Betancourt AM, Lee CW, Fan D, Wu K, Yu J, Sung JJ, Cho CH: Emerging roles of the host defense peptide LL-37 in human cancer and its potential therapeutic applications. Int J Cancer 2010; 127: 1741-1747.

Emerging roles of the host defense peptide LL‐37 in human cancer and its potential therapeutic applications

In their 2010 study published in the International Journal of Cancer, Wu et al. explore the emerging roles of the host defense peptide LL-37 in human cancer and its potential therapeutic applications. The research investigates the multifunctional properties of LL-37 in the context of cancer, including its effects on cancer cell proliferation, angiogenesis, and immune responses. The study also discusses the potential therapeutic applications of LL-37 in cancer treatment, highlighting its role as a novel candidate for cancer therapy. This research sheds light on the evolving understanding of LL-37’s involvement in cancer biology and its potential as a therapeutic target in the fight against cancer.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.25489
Wu WK, Sung JJ, To KF, Yu L, Li HT, Li ZJ, Chu KM, Yu J, Cho CH: The host defense peptide LL-37 activates the tumor-suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells. J Cell Physiol 2010; 223: 178-186.

The host defense peptide LL‐37 activates the tumor‐suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells

In their 2010 study published in the Journal of Cellular Physiology, Wu et al. investigate the impact of the host defense peptide LL-37 on bone morphogenetic protein (BMP) signaling in gastric cancer cells. The research focuses on how LL-37 activates the tumor-suppressing BMP signaling pathway by inhibiting the proteasome in these cancer cells. The study reveals a novel mechanism by which LL-37 influences intracellular signaling, leading to the suppression of gastric cancer cell growth. This research provides valuable insights into the intricate interactions between LL-37 and cellular pathways that contribute to its potential role in cancer therapy, particularly in the context of gastric cancer.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.22026
An LL, Ma XT, Yang YH, Lin YM, Song YH, Wu KF: Marked reduction of LL-37/hCAP-18, an antimicrobial peptide, in patients with acute myeloid leukemia. Int J Hematol 2005; 81: 45-7.

Marked reduction of LL-37/hCAP-18, an antimicrobial peptide, in patients with acute myeloid leukemia

In their 2005 study published in the International Journal of Hematology, An et al. report a significant reduction in LL-37/hCAP-18, an antimicrobial peptide, in patients with acute myeloid leukemia (AML). The research highlights the marked decrease in LL-37 levels in AML patients, suggesting a potential association between LL-37 and this hematological malignancy. This finding raises questions about the role of LL-37 in immune responses and its potential implications in AML. Further investigation into LL-37’s involvement in AML may provide insights into the disease’s pathogenesis and potential therapeutic avenues.

Full study on https://link.springer.com/article/10.1532/IJH97.A10407
Chen X, Qi G, Qin M, Zou Y, Zhong K, Tang Y, Guo Y, Jiang X, Liang L, Zou X: DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity. Oncotarget 2017; 8: 27943-27952.

DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity

In their 2017 study published in Oncotarget, Chen et al. explore the regulation of the human cathelicidin antimicrobial peptide gene (CAMP) promoter activity by DNA methylation. The research investigates the direct downregulation of the CAMP promoter activity through DNA methylation. The study highlights the epigenetic mechanisms that can affect the expression of cathelicidin antimicrobial peptides, such as LL-37. Understanding how DNA methylation influences CAMP expression has implications for various physiological and pathological processes, including host defense and cancer, as it may impact the antimicrobial and immunomodulatory functions of LL-37. This research sheds light on the intricate regulatory mechanisms governing LL-37 expression in different contexts.

Full study on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438620/
Piktel E, Niemirowicz K, Wnorowska U, Wątek M, Wollny T, Głuszek K, Góźdź S, Levental I, Bucki R: The role of cathelicidin LL-37 in cancer development. Arch ImmunolTherExp (Warsz) 2016; 64: 33-46.

The role of cathelicidin LL-37 in cancer development

In their 2016 review published in the Archives of Immunology and Experimental Therapy, Piktel et al. explore the multifaceted role of cathelicidin LL-37 in cancer development. The review delves into the various functions of LL-37, including its antimicrobial properties and its potential impact on cancer biology. The authors discuss the complex interplay between LL-37 and cancer, encompassing aspects such as tumor cell proliferation, angiogenesis, and metastasis. Additionally, the review addresses the immunomodulatory properties of LL-37 within the tumor microenvironment and its potential implications for cancer progression. This comprehensive study provides valuable insights into the intricate relationship between LL-37 and cancer development, emphasizing the need for further research to elucidate its precise role in oncology.

Full study on https://link.springer.com/article/10.1007/s00005-015-0359-5
Tuomela JM, Sandholm JA, Kaakinen M, Hayden KL, Haapasaari KM, Jukkola-Vuorinen A, Kauppila JH, Lehenkari PP, Harris KW, Graves DE, Selander KS: Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro. Breast Cancer Res Treat 2016; 155: 261-271.

Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro

In their 2016 study published in Breast Cancer Research and Treatment, Tuomela et al. investigate the role of telomeric G-quadruplex-forming DNA fragments in inducing invasion in breast cancer cells in vitro. The research focuses on the activation of Toll-like receptor 9 (TLR9) and the regulation of invasion by the host defense peptide LL-37. The study highlights the intricate interactions between these elements, where telomeric DNA fragments stimulate TLR9-mediated responses and LL-37 regulates the invasive behavior of breast cancer cells. These findings provide valuable insights into the complex mechanisms involved in breast cancer invasion and suggest a potential role for LL-37 in modulating tumor cell behavior in response to specific DNA structures.

Full study on https://link.springer.com/article/10.1007/s10549-016-3683-5
Ren SX, Cheng AS, To KF, Tong JH, Li MS, Shen J, Wong CC, Zhang L, Chan RL, Wang XJ, Ng SS, Chiu LC, Marquez VE, Gallo RL, Chan FK, Yu J, Sung JJ, Wu WK, Cho CH: Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Res 2012; 72: 6512-6523.

Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer

In their 2012 study published in Cancer Research, Ren et al. investigate the impact of the host immune defense peptide LL-37 on colon cancer. The research reveals that LL-37 activates caspase-independent apoptosis, a form of programmed cell death, and suppresses colon cancer cell growth. This suggests a potential role for LL-37 in inhibiting the progression of colon cancer. These findings provide insights into LL-37’s anti-cancer properties and its ability to modulate key cellular processes in colon cancer cells, highlighting its potential as a therapeutic target for colon cancer treatment.

Full study on https://aacrjournals.org/cancerres/article-abstract/72/24/6512/576212
Niemirowicz K, Prokop I, Wilczewska AZ, Wnorowska U, Piktel E, Wątek M, Savage PB, Bucki R: Magnetic nanoparticles enhance the anti-cancer activity of cathelicidin LL-37 peptide against colon cancer cells. Int J Nanomedicine 2015; 10: 3843-3853.

Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

In their 2015 study published in the International Journal of Nanomedicine, Niemirowicz et al. explore the enhanced anti-cancer activity of the cathelicidin LL-37 peptide against colon cancer cells when combined with magnetic nanoparticles. The research demonstrates that magnetic nanoparticles can augment the effectiveness of LL-37 in inhibiting colon cancer cell growth. This study offers a novel approach to enhancing the therapeutic potential of LL-37 in the context of colon cancer treatment. By combining LL-37 with magnetic nanoparticles, the researchers open up new possibilities for improving the targeted delivery and anti-cancer properties of this host defense peptide in cancer therapy.

Full study on https://www.tandfonline.com/doi/abs/10.2147/IJN.S76104
Niemirowicz K, Durnaś B, Tokajuk G, Piktel E, Michalak G, Gu X, Kułakowska A, Savage PB, Bucki R: Formulation and candidacidal activity of magnetic nanoparticles coated with cathelicidin LL-37 and ceragenin CSA-13. Sci Rep 2017; 7: 4610.

Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

In their 2017 study published in Scientific Reports, Niemirowicz et al. investigate the formulation and candidacidal (fungicidal against Candida species) activity of magnetic nanoparticles coated with two antimicrobial agents, cathelicidin LL-37 and ceragenin CSA-13. The research focuses on developing an innovative approach to combat Candida infections, a significant medical concern. By coating magnetic nanoparticles with LL-37 and CSA-13, the study demonstrates enhanced candidacidal activity, potentially offering a promising therapeutic strategy against Candida-related diseases. This research highlights the potential of combining LL-37 with nanotechnology to improve antimicrobial treatments for fungal infections.

Full study on https://www.tandfonline.com/doi/abs/10.2147/IJN.S76104
Wu WK, Sung JJ, To KF, Yu L, Li HT, Li ZJ, Chu KM, Yu J, Cho CH: The host defense peptide LL-37 activates the tumor-suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells. J Cell Physiol 2010; 223: 178-186.

The host defense peptide LL‐37 activates the tumor‐suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells

In their 2010 study published in the Journal of Cellular Physiology, Wu et al. explore the impact of the host defense peptide LL-37 on gastric cancer cells. The research demonstrates that LL-37 activates tumor-suppressing bone morphogenetic protein (BMP) signaling in gastric cancer cells by inhibiting proteasome activity. These findings suggest a potential role for LL-37 in suppressing the progression of gastric cancer by modulating BMP signaling and inhibiting proteasome-mediated degradation of tumor-suppressing proteins. This study provides valuable insights into the mechanisms through which LL-37 can exert its anti-cancer effects in the context of gastric cancer, offering potential implications for the development of novel therapeutic strategies.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.22026
Wu WK, Cho CH, Lee CW, Wu K, Fan D, Yu J, Sung JJ: Proteasome inhibition: a new therapeutic strategy to cancer treatment. Cancer Lett 2010; 293: 15-22.

Proteasome inhibition: a new therapeutic strategy to cancer treatment

In their 2010 review published in Cancer Letters, Wu et al. discuss proteasome inhibition as a promising therapeutic strategy for cancer treatment. The review highlights the importance of the proteasome in regulating protein degradation and cell cycle control, making it a potential target for cancer therapy. By inhibiting the proteasome, researchers can disrupt the degradation of specific proteins involved in cancer cell growth and survival, ultimately leading to cancer cell death. This review provides valuable insights into the potential of proteasome inhibitors as a novel approach to cancer treatment, shedding light on the development of targeted therapies for various types of cancer.

Full study on https://www.sciencedirect.com/science/article/pii/S0304383509006958
Prevete N, Liotti F, Visciano C, Marone G, Melillo RM, de Paulis A: The formyl peptide receptor 1 exerts a tumor suppressor function in human gastric cancer by inhibiting angiogenesis. Oncogene 2015; 34: 3826-3838.

The formyl peptide receptor 1 exerts a tumor suppressor function in human gastric cancer by inhibiting angiogenesis

In their 2015 study published in Oncogene, Prevete et al. investigate the role of the formyl peptide receptor 1 (FPR1) in human gastric cancer. The research reveals that FPR1 functions as a tumor suppressor in gastric cancer by inhibiting angiogenesis, the process of new blood vessel formation that is crucial for tumor growth and metastasis. FPR1 activation leads to the suppression of angiogenic factors and pathways, ultimately hindering the development of blood vessels within tumors. These findings provide insights into the potential therapeutic implications of targeting FPR1 to inhibit angiogenesis in gastric cancer, suggesting a novel approach to cancer treatment by disrupting the tumor’s blood supply.

Full study on https://www.nature.com/articles/onc2014309
Li L, Chen K, Xiang Y, Yoshimura T, Su S, Zhu J, Bian XW, Wang JM: New development in studies of formyl-peptide receptors: critical roles in host defense. J LeukocBiol 2016; 99: 425-435.

New development in studies of formyl-peptide receptors: critical roles in host defense

In their 2016 review article published in the Journal of Leukocyte Biology, Li et al. provide an overview of recent developments in the study of formyl-peptide receptors (FPRs) and their critical roles in host defense. The review highlights the importance of FPRs in the immune response, including their involvement in host defense against pathogens. FPRs are known for their ability to recognize formyl peptides, which are released by bacteria and mitochondria during infection or cellular stress. Activation of FPRs plays a crucial role in immune cell recruitment, chemotaxis, and inflammation regulation. The authors discuss the diverse functions of FPRs in various immune cells and their potential as therapeutic targets for immune-related disorders. This review provides valuable insights into the significance of FPRs in host defense mechanisms.

Full study on https://academic.oup.com/jleukbio/article-abstract/99/3/425/6935941
Mader JS, Mookherjee N, Hancock RE, Bleackley RC: The human host defense peptide LL-37 induces apoptosis in a calpain- and apoptosis-inducing factor-dependent manner involving Bax activity. Mol Cancer Res 2009; 7: 689-702.

The human host defense peptide LL-37 induces apoptosis in a calpain-and apoptosis-inducing factor–dependent manner involving bax activity

In their 2009 study published in Molecular Cancer Research, Mader et al. investigated the mechanisms by which the human host defense peptide LL-37 induces apoptosis. They found that LL-37 triggers apoptosis in a manner that involves calpain activation and the release of apoptosis-inducing factor (AIF). Additionally, Bax activity was implicated in this process. This study provides important insights into the molecular pathways through which LL-37, an antimicrobial peptide, can induce cell death, shedding light on its potential roles beyond antimicrobial defense, particularly in the context of cancer and apoptosis.

Full study on https://aacrjournals.org/mcr/article-abstract/7/5/689/90438
Yang D, Chertov O, Oppenheim JJ: Participation of mammalian defensins and cathelicidins in antimicrobial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J LeukocBiol 2001; 69: 691-697.

Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37)

The 2001 review by Yang, Chertov, and Oppenheim, titled “Participation of mammalian defensins and cathelicidins in antimicrobial immunity: receptors and activities of human defensins and cathelicidin (LL-37),” provides a comprehensive overview of the roles of human defensins and the cathelicidin LL-37 in antimicrobial immunity. It discusses the receptors and activities of these antimicrobial peptides, shedding light on their functions in host defense against microbial pathogens. This review is a valuable resource for understanding the immune responses mediated by these peptides in the context of antimicrobial defense.

Full study on https://academic.oup.com/jleukbio/article-abstract/69/5/691/6926932
Okumura K, Itoh A, Isogai E, Hirose K, Hosokawa Y, Abiko Y, Shibata T, Hirata M, Isogai H: C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells. Cancer Lett 2004; 212: 185-194.

C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells

In the study titled “C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells,” conducted by Okumura et al. in 2004, the researchers investigated the effects of the C-terminal domain of the human CAP18 antimicrobial peptide on oral squamous cell carcinoma SAS-H1 cells. Their findings revealed that this peptide induces apoptosis, or programmed cell death, in these cancer cells. This study suggests a potential therapeutic application for antimicrobial peptides in the context of cancer treatment, specifically in inducing apoptosis in oral squamous cell carcinoma cells.

Full study on https://www.sciencedirect.com/science/article/pii/S0304383504002794
Chen X, Qi G, Qin M, Zou Y, Zhong K, Tang Y, Guo Y, Jiang X, Liang L, Zou X: DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity. Oncotarget 2017; 8: 27943-27952.

DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity

In the study by Chen et al. published in 2017 titled “DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity,” the authors investigated the regulation of the CAMP gene, which encodes the human cathelicidin antimicrobial peptide LL-37, through DNA methylation. They found that DNA methylation of the CAMP promoter region directly leads to the downregulation of CAMP gene expression. This study highlights the epigenetic control of LL-37 production and its potential implications in various physiological and pathological conditions where LL-37 plays a role in host defense and immune responses. Understanding the regulation of LL-37 expression at the DNA methylation level may have implications for therapeutic interventions.

Full study on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438620/
Available from https://www.promorepharma.com/en/ll-37-healing-of-chronic-wounds/.
Ramos R, Silva JP, Rodrigues AC, et al. Wound healing activity of the human antimicrobial peptide LL37. Peptides. 2011;32(7):1469-76.

Wound healing activity of the human antimicrobial peptide LL37

The study titled “Wound healing activity of the human antimicrobial peptide LL37” by Ramos et al. investigated the potential wound healing properties of the human antimicrobial peptide LL37. The researchers conducted experiments to evaluate the effects of LL37 on wound healing in a laboratory setting. They found that LL37 exhibited wound healing activity, which suggests that this antimicrobial peptide may have therapeutic potential in promoting the healing of wounds.

Full study on https://www.sciencedirect.com/science/article/pii/S0196978111002294
Shaykhiev R, Beisswenger C, Kändler K, et al. Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L842-8.

Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure

The study titled “Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure” by Shaykhiev et al. investigated the effects of the human endogenous antibiotic LL-37 on airway epithelial cells. The researchers found that LL-37 had a stimulating effect on airway epithelial cell proliferation and wound closure. This suggests that LL-37 may play a role in promoting the repair and healing of damaged airway epithelial cells.

Full study on https://journals.physiology.org/doi/abs/10.1152/ajplung.00286.2004
Carretero M, Escámez MJ, García M, et al. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol. 2008;128(1):223-36.

In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37

The study titled “In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37” by Carretero et al. investigated the wound healing properties of the human cathelicidin LL-37 both in vitro and in vivo. The researchers found that LL-37 exhibited wound healing-promoting activities, contributing to the repair and closure of wounds. This suggests that LL-37 has potential applications in promoting wound healing and tissue repair.

Full study on https://www.sciencedirect.com/science/article/pii/S0022202X15336071
Heilborn JD, Nilsson MF, Kratz G, et al. J Invest Dermatol. 2003;120:379–389.

The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium

The study by Heilborn et al. published in the Journal of Investigative Dermatology in 2003, titled “The Cathelicidin Antimicrobial Peptide LL-37 is Involved in Re-Epithelialization of Human Skin Wounds,” investigated the role of the cathelicidin antimicrobial peptide LL-37 in the re-epithelialization of human skin wounds. The research found that LL-37 plays a role in the wound healing process, particularly in the re-epithelialization phase, where it contributes to the closure of skin wounds.

Full study on https://www.sciencedirect.com/science/article/pii/S0022202X15301913
Saporito P, Vangmouritzen M, Løbner-olesen A, Jenssen H. LL-37 fragments have antimicrobial activity against Staphylococcus epidermidis biofilms and wound healing potential in HaCaT cell line. J Pept Sci. 2018;24(7):e3080.

LL‐37 fragments have antimicrobial activity against Staphylococcus epidermidis biofilms and wound healing potential in HaCaT cell line

The study conducted by Saporito et al., published in the Journal of Peptide Science in 2018, titled “LL-37 Fragments have Antimicrobial Activity Against Staphylococcus epidermidis Biofilms and Wound Healing Potential in HaCaT Cell Line,” explored the antimicrobial activity of LL-37 fragments against Staphylococcus epidermidis biofilms and their potential for promoting wound healing in HaCaT cell line. The research found that LL-37 fragments exhibited antimicrobial activity against biofilms formed by Staphylococcus epidermidis, a common pathogen associated with biofilm-related infections. Additionally, these LL-37 fragments showed potential in promoting wound healing in HaCaT cell lines.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/psc.3080
Duplantier AJ, van Hoek ML. The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds. Front Immunol. 2013;4:143. Published 2013 Jul 3. doi:10.3389/fimmu.2013.00143.

The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds

The research article titled “The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds,” authored by Duplantier AJ and van Hoek ML, was published in Frontiers in Immunology in 2013. This study investigated the potential use of the human cathelicidin antimicrobial peptide LL-37 as a treatment for polymicrobial infected wounds. The research explored the antimicrobial properties of LL-37 and its ability to combat infections caused by a mixture of different microorganisms commonly found in wound infections. The findings suggested that LL-37 could be a promising candidate for the treatment of polymicrobial infected wounds.

Full study on https://www.frontiersin.org/articles/10.3389/fimmu.2013.00143/full
Grönberg A, Mahlapuu M, Ståhle M, Whately-smith C, Rollman O. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen. 2014;22(5):613-21.

Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial

The study titled “Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial” was conducted by Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, and Rollman O. It was published in the journal Wound Repair and Regeneration in 2014. This randomized clinical trial aimed to assess the safety and effectiveness of LL-37 in promoting the healing of hard-to-heal venous leg ulcers. The results indicated that treatment with LL-37 was both safe and effective in enhancing the healing process of these challenging wounds.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1111/wrr.12211
Edfeldt K, Agerberth B, Rottenberg ME, Gudmundsson GH, Wang XB, Mandal K, Xu Q, Yan ZQ. Involvement of the antimicrobial peptide LL-37 in human atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1551-7. doi: 10.1161/01.ATV.0000223901.08459.57. Epub 2006 Apr 27. PMID: 16645154..

Involvement of the antimicrobial peptide LL-37 in human atherosclerosis

This reference is for a scientific article published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology in July 2006. The article, authored by Edfeldt K, Agerberth B, Rottenberg ME, Gudmundsson GH, Wang XB, Mandal K, Xu Q, Yan ZQ, explores the role of the antimicrobial peptide LL-37 in the development of human atherosclerosis. LL-37 is part of the human body’s innate immune system, known for its broad-spectrum antimicrobial activity. This study suggests a link between LL-37 and atherosclerosis, a disease characterized by the buildup of fats, cholesterol, and other substances in and on artery walls (plaque), which can restrict blood flow.

Full study on https://www.ahajournals.org/doi/abs/10.1161/01.ATV.0000223901.08459.57
Bei Y, Pan LL, Zhou Q, Zhao C, Xie Y, Wu C, Meng X, Gu H, Xu J, Zhou L, Sluijter JPG, Das S, Agerberth B, Sun J, Xiao J. Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury. BMC Med. 2019 Feb 20;17(1):42. doi: 10.1186/s12916-019-1268-y. PMID: 30782145; PMCID: PMC6381635.

Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury

The citation you’ve provided refers to a research article published in BMC Medicine in February 2019. The study, conducted by Bei Y, Pan LL, Zhou Q, Zhao C, Xie Y, Wu C, Meng X, Gu H, Xu J, Zhou L, Sluijter JPG, Das S, Agerberth B, Sun J, Xiao J, investigates the protective effects of cathelicidin-related antimicrobial peptide (CRAMP) against myocardial ischemia/reperfusion (I/R) injury.

Cathelicidin-related antimicrobial peptides, similar to LL-37 in humans, are a part of the innate immune system, known for their antimicrobial properties as well as their role in modulating inflammation. Myocardial ischemia/reperfusion injury is a significant complication of acute myocardial infarction, characterized by tissue damage and inflammation when blood supply returns to the tissue after a period of ischemia or lack of oxygen.

Full study on https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1268-y
Zhou Q, Pan LL, Xue R, et al. The anti-microbial peptide LL-37/CRAMP levels are associated with acute heart failure and can attenuate cardiac dysfunction in multiple preclinical models of heart failure. Theranostics. 2020;10(14):6167-6181. Published 2020 May 15. doi:10.7150/thno.46225.

The anti-microbial peptide LL-37/CRAMP levels are associated with acute heart failure and can attenuate cardiac dysfunction in multiple preclinical models of heart failure.

This reference points to a study published in Theranostics in 2020, authored by Zhou Q, Pan LL, Xue R, et al., focusing on the antimicrobial peptide LL-37 (human) / CRAMP (mouse) in the context of acute heart failure. The study highlights that the levels of LL-37/CRAMP are associated with acute heart failure and presents evidence that this peptide can attenuate cardiac dysfunction in various preclinical models of heart failure.

The antimicrobial peptides LL-37 in humans and its murine equivalent CRAMP are recognized for their role in the innate immune system, providing a first line of defense against pathogens through their antimicrobial properties. Beyond their antimicrobial functions, these peptides have been found to possess immunomodulatory activities, which can influence inflammation, wound healing, and immune cell recruitment.

Full study on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255020/
Qin X, Zhu G, Huang L, Zhang W, Huang Y, Xi X. LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury. J Cell Biochem. 2019 Apr;120(4):4863-4871. doi: 10.1002/jcb.27641. Epub 2018 Dec 9. PMID: 30537236.

LL‐37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis‐induced acute lung injury

This citation refers to a research article published in Journal of Cellular Biochemistry in April 2019, authored by Qin X, Zhu G, Huang L, Zhang W, Huang Y, Xi X. The study focuses on the antimicrobial peptide LL-37 and its analog FF/CAP18, investigating their effects on neutrophil migration in the context of sepsis-induced acute lung injury (ALI).

Sepsis-induced ALI is a critical condition characterized by widespread inflammation in the lungs, leading to severe respiratory distress. It is often exacerbated by the excessive recruitment of neutrophils, a type of white blood cell that plays a crucial role in the body’s immune response to infection. However, when neutrophils are overly activated or recruited in large numbers, they can contribute to tissue damage and increased inflammation, worsening the condition.

Full study on https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.27641
Available at https://www.jacionline.org/article/S0091-6749(06)00727-5/abstract#articleInformation.
Zhang Z, Shively JE. Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes. PLoS One. 2010 Nov 15;5(11):e13985. doi: 10.1371/journal.pone.0013985. PMID: 21085494; PMCID: PMC2981577.

Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes

The reference is for a research article published in PLoS ONE in November 2010 by Zhang Z and Shively JE. This study investigates the effects of treating monocytes with the cathelicidin-derived peptide LL-37, leading to the generation of novel bone-forming cells termed “monoosteophils.”

LL-37 is a human cathelicidin antimicrobial peptide known for its roles in the innate immune response, including direct antimicrobial activity and modulation of inflammation. Beyond these functions, research like this study explores the broader biological activities of LL-37, including its potential in regenerative medicine and tissue repair.

Full study on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013985
Yu X, Quan J, Long W, Chen H, Wang R, Guo J, Lin X, Mai S. LL-37 inhibits LPS-induced inflammation and stimulates the osteogenic differentiation of BMSCs via P2X7 receptor and MAPK signaling pathway. Exp Cell Res. 2018 Nov 15;372(2):178-187. doi: 10.1016/j.yexcr.2018.09.024. Epub 2018 Oct 1. PMID: 30287143.

LL-37 inhibits LPS-induced inflammation and stimulates the osteogenic differentiation of BMSCs via P2X7 receptor and MAPK signaling pathway

The study published in *Experimental Cell Research* on November 15, 2018, by Yu X, Quan J, Long W, and colleagues, investigates the antimicrobial peptide LL-37 and its role in inhibiting lipopolysaccharide (LPS)-induced inflammation and promoting osteogenic differentiation of bone marrow stromal cells (BMSCs) through the P2X7 receptor and MAPK signaling pathway. This research highlights LL-37’s potential beyond its known antimicrobial functions, suggesting it could mitigate inflammatory responses and enhance bone regeneration. By elucidating the mechanisms of LL-37’s action, specifically its interaction with the P2X7 receptor and activation of the MAPK pathway, the study opens up new avenues for therapeutic applications in treating inflammatory diseases and bone-related disorders, showcasing the peptide’s versatility in modulating inflammation and tissue repair processes. The findings, detailed under DOI 10.1016/j.yexcr.2018.09.024, provide valuable insights into leveraging LL-37 for medical treatments, emphasizing its significance in immune modulation and regenerative medicine.

Full study on https://www.sciencedirect.com/science/article/pii/S001448271830572X
Supanchart C, Thawanaphong S, Makeudom A, Bolscher JG, Nazmi K, Kornak U, Krisanaprakornkit S. The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis. J Dent Res. 2012 Nov;91(11):1071-7. doi: 10.1177/0022034512460402. Epub 2012 Sep 13. PMID: 22983411.

The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis

The study by Supanchart C, Thawanaphong S, Makeudom A, and colleagues, published in the *Journal of Dental Research* in November 2012, focuses on the antimicrobial peptide LL-37 and its effects on osteoclastogenesis, the process by which osteoclasts, the cells responsible for bone resorption, are formed. The research demonstrates that LL-37 inhibits osteoclastogenesis in vitro, suggesting a potential role for this peptide in regulating bone metabolism and preventing bone loss. This finding is significant as it indicates that LL-37, known primarily for its antimicrobial and immunomodulatory functions, may also play a role in bone health by impacting the balance between bone formation and resorption. The inhibition of osteoclastogenesis by LL-37 could have therapeutic implications for conditions characterized by excessive bone loss, such as osteoporosis. The study, available under DOI 10.1177/0022034512460402, adds to the growing body of evidence on the multifunctional nature of LL-37, highlighting its potential as a target for the development of new treatments for bone-related diseases.

Full study on https://journals.sagepub.com/doi/abs/10.1177/0022034512460402
Kittaka M, Shiba H, Kajiya M, Fujita T, Iwata T, Rathvisal K, Ouhara K, Takeda K, Fujita T, Komatsuzawa H, Kurihara H. The antimicrobial peptide LL37 promotes bone regeneration in a rat calvarial bone defect. Peptides. 2013 Aug;46:136-42. doi: 10.1016/j.peptides.2013.06.001. Epub 2013 Jun 12. PMID: 23770151.

The antimicrobial peptide LL37 promotes bone regeneration in a rat calvarial bone defect

The research conducted by Kittaka M, Shiba H, Kajiya M, and their team, published in *Peptides* in August 2013, explores the role of the antimicrobial peptide LL37 in bone regeneration. Their study, using a rat calvarial bone defect model, demonstrates that LL37 significantly promotes bone healing and regeneration. This finding is particularly notable as it underscores LL37’s potential beyond its established antimicrobial and immunomodulatory functions, highlighting its capability to enhance bone repair processes. The study suggests that LL37 could be a valuable therapeutic agent for bone regeneration, offering promising implications for the treatment of bone defects and injuries. The effectiveness of LL37 in promoting bone regeneration in this preclinical model opens avenues for further research into its mechanisms of action and potential applications in regenerative medicine and dentistry. The publication, accessible via DOI 10.1016/j.peptides.2013.06.001, provides critical insights into the multifunctional role of LL37 in tissue healing and regeneration, positioning it as a candidate for developing new strategies for enhancing bone repair.

Full study on https://www.sciencedirect.com/science/article/pii/S0196978113002180
He Y, Mu C, Shen X, Yuan Z, Liu J, Chen W, Lin C, Tao B, Liu B, Cai K. Peptide LL-37 coating on micro-structured titanium implants to facilitate bone formation in vivo via mesenchymal stem cell recruitment. Acta Biomater. 2018 Oct 15;80:412-424. doi: 10.1016/j.actbio.2018.09.036. Epub 2018 Sep 25. PMID: 30266635.

Peptide LL-37 coating on micro-structured titanium implants to facilitate bone formation in vivo via mesenchymal stem cell recruitment

The study by He Y, Mu C, Shen X, and colleagues, published in *Acta Biomaterialia* on October 15, 2018, investigates the use of the antimicrobial peptide LL-37 as a coating on micro-structured titanium implants to enhance bone formation in vivo. The research focuses on LL-37’s ability to facilitate bone regeneration by recruiting mesenchymal stem cells (MSCs) to the implant site. This approach leverages LL-37’s properties not just for its antimicrobial capabilities but also for its role in cell signaling and tissue regeneration. By coating titanium implants with LL-37, the study demonstrates a novel strategy to improve osseointegration, which is critical for the success of dental and orthopedic implants. The findings suggest that LL-37 coated implants could promote better bone healing and integration by attracting MSCs, which are key players in bone regeneration. This research opens up new avenues for enhancing the performance of bone implants through bioactive coatings that support tissue healing and integration, offering promising implications for the development of improved implantable devices for bone repair and regeneration. The publication, available via DOI 10.1016/j.actbio.2018.09.036, provides valuable insights into the potential of utilizing bioactive peptides like LL-37 to improve the outcomes of surgical implants in orthopedics and dentistry.

Full study on https://www.sciencedirect.com/science/article/pii/S1742706118305658

Other Peptides

Success Stories

before after

At the age of 60, I look and feel better than I ever have in my entire life! Switching my health program and hormone replacement therapy regimen over to Genemedics was one of the best decisions I’ve ever made in my life! Genemedics and Dr George have significantly improved my quality of life and also dramatically improved my overall health. I hav...
Nick Cassavetes ,60 yrs old Movie Director (“The Notebook”, “John Q”, “Alpha Dog”), Actor and Writer

See All Men’s Testimonials

Before After

I am now in my mid-sixties and feel better than I did in my 20’s. Many people have commented that I actually look 20 years younger since I started the program at Genemedics. Calling Dr. George has proven to be one of the best decisions I have made in my life. Doctors and society convince us that developing various health issues and negative sy...
Pamela Hill ,66 yrs old

See All Women’s Testimonials

Call 800-277-4041 for a Free Consultation

What to expect during your consultation:

Usually takes 15-30 minutes
Completely confidential
No obligation to purchase anything
We will discuss your symptoms along with your health and fitness goals
Free post-consult access for any additional questions you may have

Genemedics® Health Institute is a global premier institute dedicated to revolutionizing health and medicine through healthy lifestyle education, guidance and accountability in harmony with functional medicine. Our physician-supervised health programs are personally customized to help you reach your health and fitness goals while looking and feeling better than ever.

280 North Old Woodward Ave. Suite 210 Birmingham MI 48009,USA

800-277-4041

info@genemedics.com

All Peptides

Categories

All Guides

Book a Free Consultation

Table of Contents