Expression of human cathelicidin peptide LL‐37 in inflammatory bowel disease

Abstract Cathelicidin peptide LL-37 plays an important role in the early host response against invading pathogens via its broad-spectrum antimicrobial activity. In this study, we investigated LL-37 expression in the inflamed mucosa of IBD patients. Furthermore, the regulatory mechanism of LL-37 induction was investigated in human colonic subepithelial myofibroblasts (SEMFs). LL-37 mRNA expression and protein secretion were analyzed using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Intracellular signaling pathways were analyzed using immunoblotting and specific small interference RNA (siRNA). The expression of LL-37 mRNA was significantly increased in the inflamed mucosa of ulcerative colitis and Crohn's disease. The toll-like receptor (TLR) 3 ligand, polyinosinic-polycytidylic acid (Poly(I:C)), induced LL-37 mRNA expression and stimulated LL-37 secretion in colonic SEMFs. The transfection of siRNAs specific for intracellular signaling proteins (TRIF, TRAF6, TAK1) significantly suppressed the Poly(I:C)-induced LL-37 mRNA expression. Poly(I:C) induced phosphorylation of mitogen-activated protein kinases (MAPKs) and activated nuclear factor kappa B (NF-κB) and AP-1. siRNAs specific for NF-κB and c-Jun inhibited Poly(I:C)-induced LL-37 mRNA expression. LL-37 significantly suppressed lipopolysaccharide (LPS)-induced IL-6 and IL-8 expression in colonic SEMFs. The expression of LL-37 was upregulated in the inflamed mucosa of IBD patients. LL-37 was induced by TLR3 stimulation and exhibited an anti-microbial effect via interaction with LPS. This article is protected by copyright. All rights reserved.