title: Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines.
abstract: Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases worldwide, causing fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. In the past few decades, significant progress has been made in our understanding of the molecular mechanisms underlying alcoholic liver injury. Activation of innate immunity components such as Kupffer cells, LPS/TLR4, and complements in response to alcohol exposure plays a key role in the development and progression of alcoholic liver disease (ALD). LPS activation of Kupffer cells also produces IL-6 and IL-10 that may play a protective role in ameliorating ALD. IL-6 activates signal transducer and activator of transcription 3 (STAT3) in hepatocytes and sinusoidal endothelial cells, while IL-10 activates STAT3 in Kupffer cells/macrophages, subsequently protecting against ALD. In addition, alcohol consumption also inhibits some components of innate immunity such as natural killer (NK) cells, a type of cells that play key roles in anti-viral, anti-tumor, and anti-fibrotic defenses in the liver. Ethanol inhibition of NK cells likely contributes significantly to the pathogenesis of ALD. Understanding the roles of innate immunity and cytokines in alcoholic liver injury may provide insight into novel therapeutic targets in the treatment of alcoholic liver disease.
authors.affiliation: Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Miller
authors.forename: Norio
authors.initials: N
authors.lastname: Horiguchi
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Jeong
authors.forename: Svetlana
authors.initials: S
authors.lastname: Radaeva
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology; D000437:Alcoholism / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human