LL-37 10 mg

LL-37, also known as cathelicidin antimicrobial peptide (CAMP), is a 37-amino acid cationic peptide derived from the human cationic antimicrobial protein (hCAP18). It plays a crucial role in the innate immune system, exhibiting broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. LL-37 also possesses immunomodulatory functions, influencing inflammation and wound healing processes.

LL-37 Research

LL-37 and Inflammatory Diseases

LL-37, primarily known as an antimicrobial peptide, also plays significant roles in several inflammatory diseases, including psoriasis, lupus, rheumatoid arthritis, and atherosclerosis. Depending on the local inflammatory environment and the types of cells involved, LL-37 exhibits various immune-modulating activities. It has been observed to:

• Decrease keratinocyte apoptosis,
• Increase interferon-alpha (IFN-α) production,
• Modify chemotaxis of neutrophils and eosinophils,
• Downregulate signaling through toll-like receptor 4 (TLR4),
• Increase interleukin-18 (IL-18) production, and
• Decrease levels of atherosclerotic plaques.

Interestingly, LL-37 does not consistently affect the immune system in the same way. Cell culture studies show that immune cells’ responses to LL-37 depend on their activation state; for example, T-cells increase inflammatory activity when inactive but reduce it when already activated. This suggests LL-37 has potent homeostatic effects, balancing immune responses and preventing excessive inflammation during infection. Such properties imply LL-37 may help regulate unchecked inflammation seen in autoimmune diseases. While earlier hypotheses proposed LL-37 as a causative agent in autoimmune inflammation, recent evidence indicates that elevated LL-37 levels in these diseases might actually limit more severe inflammation.

LL-37 Is a Potent Antimicrobial

As part of the innate immune system, LL-37 is among the first defenses activated during infection. Studies of skin infections reveal that normal skin maintains very low LL-37 levels, but these rise rapidly when pathogens invade. LL-37 works synergistically with other antimicrobial proteins, such as human beta-defensin 2, to fight infections.

LL-37 primarily targets bacterial lipopolysaccharide (LPS), a crucial component of the outer membrane of gram-negative bacteria. Its ability to bind and disrupt LPS makes LL-37 highly effective against these bacteria. There is ongoing interest in using LL-37 therapeutically to treat serious bacterial infections.

Although LL-37’s action is primarily on gram-negative bacteria, it also demonstrates strong effects against gram-positive bacteria like Staphylococcus aureus. In vitro research shows that LL-37 enhances the activity of lysozyme, an enzyme that destroys gram-positive bacteria.

LL-37 and Lung Disease

LPS is not unique to bacteria; it can become airborne via contamination by mold or fungi. When inhaled, LPS triggers a lung tissue response, but this is often insufficient to prevent toxic dust syndrome and respiratory diseases like asthma and COPD. Research is underway exploring LL-37 as an inhaled therapy for toxic dust syndrome.

Importantly, LL-37 promotes epithelial cell proliferation and wound closure in lung tissue. It attracts airway epithelial cells to injury sites, fostering both tissue repair and angiogenesis to supply nutrients to new tissue. LL-37 acts as a homeostatic regulator in the airways, much like its role in immune function.

Understanding LL-37 in Arthritis

LL-37 is found in high concentrations in joints affected by rheumatoid arthritis (RA). While linked to arthritis pathology, it is unclear whether LL-37 contributes to disease causation or is upregulated as a protective response. Evidence favors a protective role:

• LL-37 or other cathelicidins are not directly involved in initiating inflammatory diseases.
• LL-37 deficiency does not alter disease progression in animal models of arthritis or lupus.
• Reactivity against cathelicidins in arthritis likely results from their overexpression in inflamed tissues and is considered incidental.

Mouse studies show that LL-37-derived peptides protect against collagen damage typical of inflammatory arthritis. Administering these peptides to affected joints reduced disease severity and antibody levels against type II collagen. LL-37 also modulates inflammation driven by interleukin-32, a molecule associated with arthritis severity.

Arthritis is linked to increased expression of toll-like receptor 3 (TLR3) on synovial fibroblasts, which aggravates inflammation. LL-37 binds TLR4 and can promote either pro- or anti-inflammatory effects; ongoing research aims to clarify its role in contexts of TLR upregulation. Notably, LL-37 has been shown to selectively reduce pro-inflammatory macrophage responses.

LL-37 and the Intestine

In intestinal cell cultures, LL-37 enhances migration of cells essential for maintaining the epithelial barrier and reduces apoptosis during inflammation. These properties suggest LL-37 may serve as an adjuvant treatment for inflammatory bowel diseases, post-intestinal surgery recovery, and acute intestinal infections. It may also aid antibiotic therapies by mitigating gastrointestinal side effects.

LL-37 works synergistically with human beta-defensin 2 to repair and maintain intestinal epithelium while reducing TNF-related cell death. Since TNF-alpha inhibitors—commonly used in inflammatory bowel disease—pose risks such as increased infections, LL-37-based therapies could reduce reliance on these drugs and improve patient outcomes.

LL-37 and Intestinal Cancer

LL-37 research in cancer shows mixed results, but the peptide appears beneficial in intestinal and gastric cancers, including oral squamous cell carcinoma linked to smoking and tobacco use. These anti-cancer effects are mediated via a vitamin D-dependent pathway, potentially explaining the association between vitamin D supplementation and reduced gastrointestinal cancer risk. Vitamin D induces LL-37’s anti-cancer activity in tumor-associated macrophages.

LL-37 and Blood Vessel Growth

LL-37 stimulates prostaglandin E2 (PGE2) synthesis in endothelial cells. PGE2 is involved in inflammatory pain and angiogenesis, but its effects depend on the tissue context. In endothelial cells, PGE2 promotes blood vessel development.

Regulating angiogenesis is critical in cancer, heart disease, stroke, wound healing, and more. LL-37 provides a valuable tool for studying angiogenesis and developing interventions to either promote blood vessel growth (e.g., in heart disease) or inhibit it when harmful (e.g., cancer).

LL-37’s structure differs in humans compared to other mammals, leading to functional differences. This makes LL-37 a compelling subject for studying how amino acid sequence and 3D configuration influence receptor binding, advancing protein engineering for tailored therapeutic effects.

Research Applications

LL-37 10 mg is utilized in scientific studies focusing on:

• Antimicrobial Mechanisms: Investigating its direct bactericidal effects and interactions with microbial membranes.
• Innate Immunity: Exploring its role in modulating immune responses and influencing cytokine production.
• Wound Healing: Assessing its potential to promote tissue regeneration and repair.
• Anti-Biofilm Activity: Studying its efficacy against biofilm-forming pathogens.

Product Specifications

• Form: Lyophilized (freeze-dried) powder for reconstitution.
• Dosage: Each vial contains 10 mg of LL-37.
• Purity: ≥95%, ensuring high-quality material for research purposes.
• Packaging: Sealed vials to maintain product integrity.
• Storage: Store in a cool, dry place away from direct sunlight. After reconstitution, store at 4°C and use within 2-7 days.

Safety and Handling

LL-37 10 mg 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.

Referenced Citations

• 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-cell 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, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37,” Antimicrob. Agents Chemother., vol. 49, no. 7, pp. 2845–2850, Jul. 2005. 
• X. Chen et al., “Synergistic effect of antibacterial agents human β-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. 289, no. 5, pp. L842–848, Nov. 2005. 
• M.H. Hoffmann et al., “The cathelicidins LL-37 and CRAMP are associated with pathogenic events of arthritis in humans and rats,” Ann. Rheum. Dis., vol. 72, no. 7, pp. 1239–1248, Jul. 2013. 
• D. Kienhofer 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 1G-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, S. Napper, and N. Mookherjee, “Human cathelicidin LL-37 and its derivative 1-19 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 Salvado 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.