In mouse models of gut inflammation, giving the natural antimicrobial peptide LL‑37 (or its mouse version) lowered the amount of collagen that builds up during fibrosis. The same anti‑fibrotic effect was seen in human colon fibroblast cells in a dish, where LL‑37 blocked collagen production triggered by growth factors. This suggests LL‑37 can directly stop scar‑forming processes in the gut, at least in animals and cells.

Cathelicidin (LL-37 in human and mCRAMP in mice) represents a family of endogenous antimicrobial peptides with anti-inflammatory effects. LL-37 also suppresses collagen synthesis, an important fibrotic response, in dermal fibroblasts. Here we determined whether exogenous cathelicidin administration modulates intestinal fibrosis in two animal models of intestinal inflammation and in human colonic fibroblasts. C57BL/6J mice (n=6 per group) were administered intracolonically with a trinitrobenzene sulphonic acid (TNBS) enema to induce chronic (6-7 weeks) colitis with fibrosis. mCRAMP peptide (5 mg/kg every 3 day, week 5-7) or cathelicidin gene (<i>Camp</i>)-expressing lentivirus (10⁷ infectious units week 4) were administered intracolonically or intravenously, respectively. 129Sv/J mice were infected with <i>Salmonella typhimurium</i> orally to induce cecal inflammation with fibrosis. <i>Camp</i> expressing lentivirus (10⁷ infectious units day 11) was administered intravenously. TNBS-induced chronic colitis was associated with increased colonic collagen (col1a2) mRNA expression. Intracolonic cathelicidin (mCRAMP peptide) administration or intravenous delivery of lentivirus-overexpressing cathelicidin gene significantly reduced colonic col1a2 mRNA expression in TNBS-exposed mice, compared to vehicle administration. <i>Salmonella</i> infection also caused increased cecal inflammation associated with collagen (col1a2) mRNA expression that was prevented by intravenous delivery of <i>Camp</i>-expressing lentivirus. Exposure of human primary intestinal fibroblasts and human colonic CCD-18Co fibroblasts to transforming growth factor-beta1 (TGF-beta1) and/or insulin-like growth factor 1 induced collagen protein and mRNA expression, that was reduced by LL-37 (3-5 &#xb5;M) through a MAP kinase-dependent mechanism. Cathelicidin can reverse intestinal fibrosis by directly inhibiting collagen synthesis in colonic fibroblasts.