Cathelicidins

Cathelicidins are a family of endogenous antimicrobial peptides characterized by a conserved N-terminal cathelin domain and a variable C-terminal antimicrobial peptide. LL-37 is the sole human cathelicidin — a 37-amino acid cationic peptide with broad-spectrum antimicrobial, wound-healing, and immunomodulatory activity. Research interest spans topical antimicrobials, chronic wound care, and cancer biology.

LL-37 disrupts bacterial membranes via amphipathic alpha-helix insertion, causing membrane depolarization and lysis. It also binds lipopolysaccharide (LPS), neutralizing endotoxin. Beyond direct killing, LL-37 activates keratinocyte migration through formyl peptide receptor 2 (FPR2), triggering MAPK and PI3K/Akt signaling. It promotes angiogenesis by activating VEGFR2, and recruits neutrophils, monocytes, and T cells via FPR1. In wounds, LL-37 accelerates re-epithelialization and vascularization and is notably absent in chronic non-healing ulcers.

LL-37 is found in neutrophil granules, keratinocytes, lung epithelium, and intestinal Paneth cells. Studies demonstrate that topical LL-37 accelerates healing of chronic wounds in diabetic and venous ulcer models. It shows activity against MRSA, Pseudomonas aeruginosa, and biofilms. In vitro and early-phase clinical data support its role in wound management. Paradoxically, overexpression is linked to inflammatory skin diseases (rosacea, psoriasis) and certain cancers, where LL-37 acts as a growth factor. No LL-37 drug is currently FDA-approved; clinical trials are ongoing.

Peptides commonly paired with Cathelicidins for synergistic effects.