title: Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection.
abstract: Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. Cathelicidin peptides suppress intestinal inflammation and improve intestinal epithelial barrier function independently of their antimicrobial activity. In this study, we investigated the effects of Cathelicidin-WA (CWA) on intestinal epithelial barrier function, as well as the underlying mechanism, by using enterohemorrhagic Escherichia coli (EHEC)-infected mice and intestinal epithelial cells. The results showed that CWA attenuated EHEC-induced clinical symptoms and intestinal colitis, as did enrofloxacin (Enro). CWA decreased IL-6 production in the serum, jejunum, and colon of EHEC-infected mice. Additionally, CWA alleviated the EHEC-induced disruption of mucin-2 and goblet cells in the intestine. Interestingly, CWA increased the mucus layer thickness, which was associated with increasing expression of trefoil factor 3, in the jejunum of EHEC-infected mice. CWA increased the expression of tight junction proteins in the jejunum of EHEC-infected mice. Using intestinal epithelial cells and a Rac1 inhibitor in vitro, we demonstrated that the CWA-mediated increases in the tight junction proteins might depend on the Rac1 pathway. Furthermore, CWA improved the microbiota and short-chain fatty acid concentrations in the cecum of EHEC-infected mice. Although Enro and CWA had similar effects on intestinal inflammation, CWA was superior to Enro with regard to improving intestinal epithelial barrier and microbiota in the intestine. In conclusion, CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases.
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; and.|Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong 510640, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yi
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; and.
authors.forename: Wangyang
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; and.
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; and yzwang321@zju.edu.cn zqlu2012@163.com 751886825@qq.com.
authors.forename: Zeqing
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China; and yzwang321@zju.edu.cn zqlu2012@163.com 751886825@qq.com.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D054804:Cathelicidins / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D054324:Enterohemorrhagic Escherichia coli / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D051379:Mice; D064307:Microbiota / Q000187:drug effects; D055262:Mucin-2 / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000071165:Trefoil Factor-3 / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D054804:Cathelicidins; D015850:Interleukin-6; D055262:Mucin-2; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3; C577686:interleukin-6, mouse; D020830:rac1 GTP-Binding Protein