Document Detail


Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease.
MedLine Citation:
PMID:  22320924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The activation of innate immunity by various factors (e.g. lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro-inflammatory cytokines (e.g. tumor necrosis factor [TNF]-α) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10 during alcoholic liver injury. IL-6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL-10 may play a dual role in controlling ethanol-induced steatosis and liver injury via the inhibition of the pro-inflammatory cytokine TNF-α, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL-6, thereby potentiating alcoholic liver injury. IL-22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a receptor complex composed of IL-10R2 and IL-22R chains on the surfaces of hepatocytes. Finally, IL-22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects.
Authors:
Bin Gao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review    
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  27 Suppl 2     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-10     Completed Date:  2012-06-06     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  89-93     Citation Subset:  IM    
Copyright Information:
Published © 2012 This article is a U.S. Government work and is in the public domain in the USA.
Affiliation:
Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. bgao@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / therapeutic use*
Cytokines / metabolism,  therapeutic use*
Cytoprotection
Humans
Immunity, Innate / drug effects
Inflammation Mediators / metabolism
Interleukin-10 / metabolism
Interleukin-6 / metabolism
Interleukins / metabolism,  therapeutic use
Kupffer Cells / drug effects,  immunology
Liver / drug effects*,  immunology,  pathology
Liver Diseases, Alcoholic / drug therapy*,  immunology,  pathology
STAT3 Transcription Factor / metabolism
Treatment Outcome
Grant Support
ID/Acronym/Agency:
Z99 AA999999/AA/NIAAA NIH HHS; ZIA AA000369-10/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cytokines; 0/Inflammation Mediators; 0/Interleukin-6; 0/Interleukins; 0/STAT3 Transcription Factor; 0/interleukin-22; 130068-27-8/Interleukin-10
Comments/Corrections

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