| Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. | |
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MedLine Citation:
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PMID: 22093263 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yuhua Wang; Irina Kirpich; Yanlong Liu; Zhenhua Ma; Shirish Barve; Craig J McClain; Wenke Feng |
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Publication Detail:
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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:
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Title: The American journal of pathology Volume: 179 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-18 Completed Date: 2012-02-09 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2866-75 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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College of Food Science and Engineering, Jilin Agricultural University, Changchun, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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:
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Am J Pathol. 2012 Jan;180(1):429-30 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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