Cathelicidin-BF ameliorates lipopolysaccharide-induced intestinal epithelial barrier disruption in rat

Abstract

AimsThe present study examined the effect of the antimicrobial peptide cathelicidin-BF (CBF) on LPS-induced mucosal injury and intestinal epithelial barrier dysfunction in a rat model and in the porcine intestinal epithelial cell line. Main methodsChanges in barrier integrity were assessed in intestinal epithelium and IPEC-J2 monolayers by measuring nutrient absorption and transepithelial electrical resistance (TER), and the permeability of intestinal epithelium was examined by measuring plasma d-lactate and diamine oxidase levels. The expression levels of tight junction (TJ) proteins were quantified by real-time PCR, and immunofluorescence was used to analyse the location and distribution of TJs in cells. Key findingsIn vivo, CBF improved epithelial barrier function through attenuating the alterations of the mucosal structure, nutrient absorption and TER in the jejunum, and preventing the down-regulation of TJ proteins in LPS-induced rat intestinal epithelium. In vitro, CBF prevented the disruption and the re-distribution of ZO-1 and occludin, and suppressed the increase in inflammatory cytokine levels in LPS-induced IPEC-J2. The CBF-induced upregulation of zonula occludens-1 and occludin was prevented by U0126 or SB203580, suggesting the involvement of the MEK and p38 MAPK pathways in the CBF-induced changes in tight junctions. SignificanceOur results showed that CBF prevents LPS-induced intestinal epithelial barrier dysfunction, suggesting its potential as a therapeutic agent for the prevention of LPS-mediated intestinal diseases. We found that exogenous CBF had protective effects on LPS-induced intestinal epithelial barrier disruption in rats and on epithelial damage in IPEC-J2 cells.