LL-37 (CAP-18, Cathelicidin)

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.

Key Activities

• Antimicrobial Properties: LL-37 has strong antimicrobial effects, helping to combat bacterial, viral, and fungal infections.
• Immune System Enhancement: It boosts the immune system, aiding in the body’s defense against pathogens.
• Wound Healing: LL-37 promotes wound healing by stimulating tissue regeneration and reducing inflammation.
• Anti-Inflammatory Effects: It reduces inflammation, contributing to overall health and recovery in inflammatory conditions.
• Tissue Regeneration: LL-37 supports tissue regeneration, aiding in the repair and maintenance of healthy tissues.

Chemical Structure of LL-37

LL-37 Sequence

LL-37, a human antimicrobial peptide, is composed of 37 amino acids, hence the designation “LL-37.” The sequence of LL-37 is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, a structure that plays a crucial role in its biological functions. The amphipathic nature of LL-37, with both hydrophilic and hydrophobic regions, allows it to interact with and disrupt microbial membranes, thereby exerting its potent antimicrobial effects.

The sequence of LL-37 is not only essential for its antimicrobial properties but also for its role in modulating the immune system. Specific amino acid residues within the sequence are responsible for binding to and neutralizing lipopolysaccharides (LPS), which are components of the outer membrane of Gram-negative bacteria. By neutralizing LPS, LL-37 helps to prevent excessive inflammatory responses, thus protecting the host from potential damage due to overactive immune reactions.

Furthermore, the sequence of LL-37 is involved in signaling pathways that promote wound healing and tissue regeneration. For instance, certain segments of the peptide can interact with cell surface receptors, triggering pathways that lead to increased cell proliferation and migration. This makes LL-37 a valuable component not only in the innate immune response but also in the processes of healing and tissue repair.

CAS. #: 154947-66-7

Formula: 

C₂₀₅H₃₄₀N₅₀O₅₃

M.W.: 4493.3 g/mol

Synonyms: CAP-18, Cathelicidin, antibacterial peptide LL-37

LL-37 Research

LL-37 Is a Potent Antimicrobial

LL-37 is part of the innate immune system and as such is one of the first pieces of the immune system to be activated during infection. Research in skin infections suggests that normal skin has very low levels of LL-37 but that the peptide accumulates rapidly in the presence of invading pathogens. The peptide has been shown to work in tandem with other proteins, like human beta-defensin 2 to combat infection.

LL-37 primarily works by binding to bacterial lipopolysaccharide (LPS), a major component of the outer membrane of gram-negative bacteria. LPS is a critical component of membrane integrity in these bacteria.

The ability of LL-37 to bind to and interfere with LPS means it is exceptionally deadly to certain bacteria. There is interest in using the peptide exogenously to treat serious bacterial infections in people.

Despite the fact that LL-37 acts on the cell membrane components of gram-negative bacteria, it still has potent gram-positive effects as well. This could make it a beneficial treatment for staph infections and other serious bacteria. In vitro research indicates that LL-37 enhances the effects of lysozyme, an enzyme responsible for the destruction of gram positive bacteria like Staph aureus

LL-37 and Inflammatory Diseases

LL-37, while primarily billed as an antimicrobial peptide, actually plays a role in a number of inflammatory diseases such as psoriasis, lupus, rheumatoid arthritis, and atherosclerosis. Depending on the local inflammatory environment and the particular cells involved, LL-37 has several different immune system modulating behaviors. It has been found to:

• decrease keratinocyte apoptosis;
• increase IFN-alpha production;
• alter chemotaxis of neutrophils and eosinophils,
• down-regulate signaling through toll-like receptor 4 (TLR4),
• increase IL-18 production, and
• decrease levels of atherosclerotic plaques.

Interestingly, LL-37 does not affect the immune system in the same way all of the time. Research in cell culture has shown that the inflammatory environment affects how cells of the immune system respond to LL-37. T-cells, for instance, will increase their inflammatory actions in response to LL-37 when they are not activated but decrease inflammatory action when already activated[2]. It appears that LL-37 has potent homeostatic effects, helping to balance the immune response and prevent it from becoming overactive in the setting of infection. These findings would suggest that LL-37 could play a role in helping to regulate the unchecked inflammation of autoimmune diseases. This may explain why there has been a strong correlation between LL-37 levels and autoimmune disease. It was previously thought that LL-37 might be causing autoimmune inflammation, but more recent evidence suggests that high levels of LL-37 in autoimmune disease may actually be preventing more fulminant inflammation.