title: Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.
abstract: Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis.
authors.affiliation: Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Jin-Hang
authors.initials: JH
authors.lastname: Gao
authors.affiliation: Department of Human Anatomy, Academy of Preclinical and Forensic Medicine, West China Medicine College, Sichuan University, Chengdu, China; and.
authors.forename: Shi-Lei
authors.initials: SL
authors.lastname: Wen
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Shi-Hang
authors.initials: SH
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Zhao-Ping
authors.initials: ZP
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tai
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ye
authors.affiliation: Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and.
authors.forename: Zhi-Yin
authors.initials: ZY
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Ying-Mei
authors.initials: YM
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China; and shcqcdmed@163.com.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Tang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D000068579:Celecoxib / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D000068579:Celecoxib; D015232:Dinoprostone
keywords: cyclooxygenase-2; inflammatory transport; intestinal epithelial barrier; liver cirrhosis