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Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2016 Jun 01; Vol. 310 (11), pp. G962-72. Date of Electronic Publication: 2016 Apr 07. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 the American Physiological Society.)
- Subjects :
- Animals
Caco-2 Cells
Cadherins metabolism
Celecoxib therapeutic use
Cyclooxygenase 2 metabolism
Cyclooxygenase 2 Inhibitors therapeutic use
Dinoprostone metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Humans
Interleukin-6 metabolism
Intestinal Absorption
Jejunum drug effects
Liver drug effects
Liver Cirrhosis metabolism
Rats
Rats, Sprague-Dawley
T-Lymphocytes drug effects
T-Lymphocytes immunology
Tumor Necrosis Factor-alpha metabolism
Zonula Occludens-1 Protein metabolism
Celecoxib pharmacology
Cyclooxygenase 2 Inhibitors pharmacology
Jejunum metabolism
Liver metabolism
Liver Cirrhosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 310
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 27056726
- Full Text :
- https://doi.org/10.1152/ajpgi.00428.2015