Document Detail


Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury.
MedLine Citation:
PMID:  22093263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gut-derived endotoxin is a critical factor in the development and progression of alcoholic liver disease (ALD). Probiotics can treat alcohol-induced liver injury associated with gut leakiness and endotoxemia in animal models, as well as in human ALD; however, the mechanism or mechanisms of their beneficial action are not well defined. We hypothesized that alcohol impairs the adaptive response-induced hypoxia-inducible factor (HIF) and that probiotic supplementation could attenuate this impairment, restoring barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. C57BJ/6N mice were fed the Lieber DeCarli diet containing 5% alcohol for 8 weeks. Animals received Lactobacillus rhamnosus GG (LGG) supplementation in the last 2 weeks. LGG supplementation significantly reduced alcohol-induced endotoxemia and hepatic steatosis and improved liver function. LGG restored alcohol-induced reduction of HIF-2α and intestinal trefoil factor levels. In vitro studies using the Caco-2 cell culture model showed that the addition of LGG supernatant prevented alcohol-induced epithelial monolayer barrier dysfunction. Furthermore, gene silencing of HIF-1α/2α abolished the LGG effects, indicating that the protective effect of LGG is HIF-dependent. The present study provides a mechanistic insight for utilization of probiotics for the treatment of ALD, and suggests a critical role for intestinal hypoxia and decreased trefoil factor in the development of ALD.
Authors:
Yuhua Wang; Irina Kirpich; Yanlong Liu; Zhenhua Ma; Shirish Barve; Craig J McClain; Wenke Feng
Related Documents :
21784013 - Up-regulation of rage and s100a6 in rats exposed to cigarette smoke.
3772983 - Interactions between cimetidine, methylparathion, and parathion.
17477423 - Liver and lung late alterations following hepatic reperfusion associated to ischemic pr...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  179     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-18     Completed Date:  2012-02-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2866-75     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Affiliation:
College of Food Science and Engineering, Jilin Agricultural University, Changchun, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Caco-2 Cells
Cell Membrane Permeability
Epithelial Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Ileum / metabolism
Lactobacillus rhamnosus*
Liver Diseases, Alcoholic / metabolism,  prevention & control*
Male
Mice
Mice, Inbred C57BL
Signal Transduction
Grant Support
ID/Acronym/Agency:
P01-AA017103/AA/NIAAA NIH HHS; P30-AA019360/AA/NIAAA NIH HHS; R01 AA018016/AA/NIAAA NIH HHS; R01 AA018869/AA/NIAAA NIH HHS; R01-AA015970/AA/NIAAA NIH HHS; R01-AA018016/AA/NIAAA NIH HHS; R01-AA018869/AA/NIAAA NIH HHS; R01-DK071765/DK/NIDDK NIH HHS; R37-AA010762/AA/NIAAA NIH HHS; RC2-AA019385/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/endothelial PAS domain-containing protein 1
Comments/Corrections
Erratum In:
Am J Pathol. 2012 Jan;180(1):429-30

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Quantitation of human herpesvirus-6 (HHV-6) DNA in a cord blood transplant recipient with chromosoma...
Next Document:  Intracoronary Transluminal Attenuation Gradient in Coronary CT Angiography for Determining Coronary ...