Search
Close
Search
Advanced Search
Search Menu
AI Discovery Assistant

Background

Cathelicidin (LL-37 in human and mCRAMP in mice) is a family of endogenous anti-microbial peptides that protect the host from infection as part of the innate immune response. Recent evidences suggest that cathelicidins may modulate inflammation. Here we determine whether cathelicidin can modulate colonic fibrosis in animal model of colitis as well as human colonic fibroblasts.

Methods

Wild-type and mCRAMP deficient mice were administered with trinitrobenzene sulphonic acid (TNBS) to induce chronic (7 weeks) colitis. Some mice were treated intracolonically with cathelicidin and colonic histological changes and fibrogenic mediator levels during colonic inflammation were evaluated.

Results

TNBS induced chronic colitis associated colonic fibrosis in mice that was reduced by exogenous intracolonic cathelicidin (mCRAMP) administration (5 mg/kg every 3 days). This inhibitory mCRAMP effect was associated with lower colonic histological damage and reduced levels of the fibrotic mediator collagen 1alpha2, fibroblast infiltration and proinflammatory cytokine TNFalpha levels in colon compared to controls. Exogenous mCRAMP treatment also prevented body weight loss due to chronic colitis. However, endogenous cathelicidin expression was not altered in the colons of TNBS exposed mice. There were no significant difference of TNBS-induced colonic fibrosis between wild-type mice and mCRAMP deficient mice, suggesting that endogenous cathelicidin does not play a role in the development of colitis associated fibrosis. Exposure of human colonic CCD-18Co fibroblasts to LL-37 (10 microM) significantly reduced transforming growth factor-beta1 (50 ng/mL) and insulin-like growth factor 1 (10ng/mL) induced collagen COL1A2 protein and mRNA expression. LL-37 treatment did not change basal TGF-beta1 and insulin like growth factor-1 expression in colonic CCD-18Co fibroblasts. LL-37 (10 microM) stimulated collagenase MMP1 mRNA expression in CCD-18Co which is capable for degrading extracellular matrix including collagen.

Conclusion(s)

Cathelicidins modulates chronic colitis associated colonic fibrosis by mechanisms involving inhibition of collagen expression and activation of collagenase expression in colonic fibroblasts. Our results also indicate that exogenous cathelicidin administration may represent a novel approach for treatment of colonic fibrosis in Crohn’s disease.

This content is only available as a PDF.
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Topic:
Issue Section:
Basic Science Poster Presentations
You do not currently have access to this article.
Download all slides