Feifei Han1, Zeqing Lu2, Yifan Liu2, Xi Xia2, Haiwen Zhang2, Xinxia Wang2, Yizhen Wang3. 1. Food Safety Key Laboratory of Zhejiang Province, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China. 2. Key Laboratory of Animal Nutrition and Feed Science (Hua Dong), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. 3. Key Laboratory of Animal Nutrition and Feed Science (Hua Dong), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: yzwang@zju.edu.cn.
Abstract
AIMS: The 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 METHODS: Changes 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 FINDINGS: In 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. SIGNIFICANCE: Our 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.
AIMS: The 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 METHODS: Changes 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 FINDINGS: In 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. SIGNIFICANCE: Our 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.
Authors: Ting Zhang; Shan H Lu; Qian Bi; Li Liang; Yan F Wang; Xing X Yang; Wen Gu; Jie Yu Journal: Front Pharmacol Date: 2017-11-09 Impact factor: 5.810