Title

Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells: implications for immunity

UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Date

4-24-2009

Document Type

Article

Medical Subject Headings

Alcohol Drinking; Animals; Autoimmunity; Ethanol; Fatty Liver, Alcoholic; Hepatocytes; Humans; Immunity, Innate; Inflammation Mediators; Kupffer Cells; Lipid Metabolism; Liver; Liver Diseases, Alcoholic; Signal Transduction; Toll-Like Receptor 4

Disciplines

Gastroenterology | Hepatology | Immunology and Infectious Disease

Abstract

Alcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response, inflammatory injury, and autoimmune activation. Recent developments in the literature are reviewed in a model that suggests lipid accumulation, dysregulation of immunity, and impaired antiviral and autoimmune responses as three distinct, though interwoven, pathophysiological mechanisms of alcoholic liver injury.

Rights and Permissions

Citation: Semin Liver Dis. 2009 May;29(2):166-77. Epub 2009 Apr 22. Link to article on publisher's site

Related Resources

Link to Article in PubMed