LL-37 5mg

LL-37 is a 37-amino acid antimicrobial peptide derived from the human cathelicidin precursor protein, hCAP-18. It plays a crucial role in the innate immune system by exhibiting broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. LL-37 is also involved in modulating inflammation, promoting wound healing, and regulating immune responses.

LL-37 Research

LL-37 and Its Role in Inflammatory Diseases

Though LL-37 is mainly known as an antimicrobial peptide, it also plays important roles in various inflammatory conditions including psoriasis, lupus, rheumatoid arthritis, and atherosclerosis. Its immune-modulating actions vary depending on the local inflammation and cell types involved. Key effects of LL-37 include:

• Reducing programmed cell death (apoptosis) in skin cells (keratinocytes),
• Increasing production of interferon-alpha (IFN-α),
• Modifying the movement (chemotaxis) of immune cells like neutrophils and eosinophils,
• Decreasing signaling through toll-like receptor 4 (TLR4),
• Enhancing interleukin-18 (IL-18) levels,
• Lowering the formation of atherosclerotic plaques.

Interestingly, LL-37’s immune effects are not fixed; for example, it can either increase or decrease inflammatory responses of T-cells based on whether the T-cells are activated or not. This suggests LL-37 helps maintain immune balance and prevent excessive inflammation during infections. This balancing role may explain why LL-37 levels are elevated in autoimmune diseases—not as a cause, but possibly as a protective mechanism against excessive immune activation.

LL-37 as a Potent Antimicrobial Agent

LL-37 is a crucial part of the innate immune system and acts early during infections. Normally, skin contains very low levels of LL-37, but these levels rise quickly when pathogens invade. LL-37 works alongside other antimicrobial proteins like human beta-defensin 2 to fight infections effectively.

The peptide’s primary mechanism is binding to lipopolysaccharide (LPS), a critical molecule in the outer membrane of gram-negative bacteria, disrupting bacterial integrity and killing the pathogens. Beyond gram-negative bacteria, LL-37 also enhances the action of enzymes like lysozyme that target gram-positive bacteria, making it effective against infections such as Staphylococcus aureus.

LL-37’s Role in Lung Disease

LPS is also found in airborne contaminants like mold spores, which can trigger respiratory diseases including asthma and COPD. Research into inhaled LL-37 treatment aims to protect against these conditions by boosting lung defense. Additionally, LL-37 promotes lung epithelial cell growth and wound healing by attracting these cells to injury sites and supporting blood vessel growth for tissue repair, acting as a key regulator of airway health.

LL-37 and Arthritis

In rheumatoid arthritis, LL-37 is found at high levels in affected joints. While it is unclear if LL-37 causes arthritis, evidence suggests it plays a protective role. Animal studies show that peptides derived from LL-37 reduce joint damage and inflammation. LL-37 also modulates inflammation caused by molecules linked to arthritis severity, such as interleukin-32.

LL-37 interacts with toll-like receptors (TLRs), which influence inflammation in arthritis, but whether it promotes or inhibits inflammation in this context is still under investigation. However, its selective suppression of pro-inflammatory macrophage responses supports its role in controlling inflammation.

LL-37 in Intestinal Health

LL-37 supports intestinal health by promoting the migration of cells that maintain the gut lining and reducing cell death during inflammation. This makes it a promising adjunct for treating inflammatory bowel disease (IBD), post-surgical healing, and infections. It also works alongside human beta-defensin 2 to repair intestinal tissue and reduce tumor necrosis factor-alpha (TNF-α)-related cell death, which could reduce dependence on TNF inhibitors that have serious side effects.

LL-37 and Intestinal Cancer

The relationship between LL-37 and cancer is complex, but it appears to help protect against certain intestinal and gastric cancers. Its anti-cancer activity may depend on vitamin D pathways, which could explain the protective effects of vitamin D against gastrointestinal cancers by stimulating tumor-associated macrophages via LL-37.

LL-37 and Blood Vessel Growth

LL-37 stimulates production of prostaglandin E2 (PGE2) in endothelial cells, a molecule involved in both pain and blood vessel formation (angiogenesis). The regulation of angiogenesis is critical in many diseases, including cancer, heart disease, stroke, and wound healing. LL-37 offers a useful model to explore and potentially control blood vessel growth beneficially or detrimentally, depending on the disease context.

Research Applications

LL-37 is primarily utilized in scientific studies focusing on:

• Antimicrobial Activity: Investigating its effectiveness against various pathogens, including antibiotic-resistant strains.
• Immunomodulation: Exploring its role in regulating immune responses and inflammation.
• Wound Healing: Studying its effects on tissue repair and regeneration.
• Cancer Research: Evaluating its potential in inhibiting tumor growth and metastasis.

Product Specifications

• Form: Lyophilized (freeze-dried) powder for reconstitution.
• Dosage: Each vial contains 5mg of LL-37.
• Purity: Typically ≥99%, ensuring high-quality material for research purposes.
• Packaging: Available in sealed vials containing 5mg of LL-37 powder.
• Storage: Store lyophilized LL-37 at temperatures below -18°C. After reconstitution, store at 4°C and use within 2-7 days.

Safety and Handling

LL-37 is intended strictly for laboratory research and is not approved for human consumption. Handle with care, following appropriate safety protocols. Ensure proper storage conditions to maintain the integrity and efficacy of the compound.

Selected References

• J. M. Kahlenberg and M. J. Kaplan, “Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease,” J. Immunol., vol. 191, no. 10, Nov. 2013. 
• D. S. Alexandre-Ramos et al., “LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation,” Biomed. Pharmacother., vol. 108, pp. 1584-1590, Dec. 2018. 
• P. Y. Ong et al., “Endogenous antimicrobial peptides and skin infections in atopic dermatitis,” N. Engl. J. Med., vol. 347, no. 15, pp. 1151-1160, Oct. 2002. 
• C. D. Ciomei et al., “Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization... of analogs of LL-37,” Antimicrob. Agents Chemother., vol. 49, no. 7, pp. 2845-2850, Jul. 2005. 
• X. Chen et al., “Synergistic effect of antibacterial agents human B-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli,” J. Dermatol. Sci., vol. 40, no. 2, pp. 123-132, Nov. 2005. 
• M. Golec, “Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide,” Ann. Agric. Environ. Med., vol. 14, no. 1, pp. 1-4, 2007. 
• R. Shaykhiev et al., “Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure,” Am. J. Physiol. Lung Cell. Mol. Physiol., vol. 789, no. 5, pp. L842-L848, Nov. 2005. 
• M. H. Hoffmann et al., “The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats,” Ann. Rheum. Dis., vol. 72, no. 7, pp. 1239-1248, Jul. 2013. 
• D. Kienhöfer et al., “No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis,” PLoS One, vol. 9, no. 12, p. e115474, 2014. 
• L. N. Y. Chow et al., “Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis,” Mol. Immunol., vol. 57, no. 2, pp. 86-92, Feb. 2014.
• K.-Y. G. Choi et al., “Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced inflammation,” Immunology, vol. 143, no. 1, pp. 68-80, Sep. 2014. 
• W. Zhu et al., “Arthritis is associated with T-cell-induced upregulation of Toll-like receptor 3 on synovial fibroblasts,” Arthritis Res. Ther., vol. 13, no. 3, p. R103, Jun. 2011. 
• K. L. Brown et al., “Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses,” J. Immunol., vol. 186, no. 9, pp. 5497-5505, May 2011.
• J.-M. Otte et al., “Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity,” Regul. Pept., vol. 156, no. 1-3, pp. 104-117, Aug. 2009. 
• J.-M. Otte et al., “Human beta defensin 2 promotes intestinal wound healing in vitro,” J. Cell. Biochem., vol. 104, no. 6, pp. 2286-2297, Aug. 2008. 
• X. Chen et al., “Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer,” Cell. Physiol. Biochem., vol. 47, no. 3, pp. 1060-1073, 2018. 
• M. Dolores et al., “Cathelicidin LL-37 induces angiogenesis via PGE2-EP3 signaling in endothelial cells, in vivo inhibition by aspirin,” Arterioscler. Thromb. Vasc. Biol., vol. 33, no. 8, pp. 1965-1972, Aug. 2013. 
• D. Xhindoli et al., “The human cathelicidin LL-37 — A pore-forming antibacterial peptide and host-cell modulator,” Biochim. Biophys. Acta Biomembr., vol. 1858, no. 3, pp. 546-566, Mar. 2016.