title: Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B.
abstract: OBJECTIVE
  This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis.
  
  
  RESULTS
  Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys(3)]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation.
  
  
  CONCLUSIONS
  Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction.
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Jian
authors: J
authors: Cheng
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Lin
authors: L
authors: Zhang
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Weiqi
authors: W
authors: Dai
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Yuqing
authors: Y
authors: Mao
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Sainan
authors: S
authors: Li
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Jingjie
authors: J
authors: Wang
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Huanqing
authors: H
authors: Li
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Chuanyong
authors: C
authors: Guo
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China. Electronic address: xiaomingfan57@sina.com.
authors: Xiaoming
authors: X
authors: Fan
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects
chemical_list: D016207:Cytokines; D054439:Ghrelin; D016328:NF-kappa B; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D016264:Dextran Sulfate; D009195:Peroxidase; D009219:Myosin-Light-Chain Kinase
keywords: Colitis; Dextran sulfate sodium; Ghrelin; Intestinal barrier dysfunction; Nuclear factor-kappa B