Innate immunity in alcoholic liver disease

Bin Gao, Ekihiro Seki, David A. Brenner, Scott Friedman, Jessica I. Cohen, Laura Nagy, G. Szabó, Samir Zakhari

Research output: Contribution to journalReview article

129 Citations (Scopus)

Abstract

Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume300
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Alcoholic Fatty Liver
Alcoholic Liver Diseases
Innate Immunity
Alcohol Drinking
Liver Cirrhosis
Alcohols
Hepatic Stellate Cells
Western World
Kupffer Cells
Complement Activation
Adaptive Immunity
Virus Diseases
Chronic Hepatitis
Natural Killer Cells
Liver Diseases
Oxidative Stress
Fibrosis
Chronic Disease
Liver
Therapeutics

Keywords

  • Alcoholic liver injury
  • Complement
  • NK cells
  • TLR4

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Gao, B., Seki, E., Brenner, D. A., Friedman, S., Cohen, J. I., Nagy, L., ... Zakhari, S. (2011). Innate immunity in alcoholic liver disease. American Journal of Physiology - Gastrointestinal and Liver Physiology, 300(4). https://doi.org/10.1152/ajpgi.00537.2010

Innate immunity in alcoholic liver disease. / Gao, Bin; Seki, Ekihiro; Brenner, David A.; Friedman, Scott; Cohen, Jessica I.; Nagy, Laura; Szabó, G.; Zakhari, Samir.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 300, No. 4, 04.2011.

Research output: Contribution to journalReview article

Gao, Bin ; Seki, Ekihiro ; Brenner, David A. ; Friedman, Scott ; Cohen, Jessica I. ; Nagy, Laura ; Szabó, G. ; Zakhari, Samir. / Innate immunity in alcoholic liver disease. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2011 ; Vol. 300, No. 4.
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