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Article
Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells: implications for immunity
Gastroenterology Publications and Presentations
  • Bharath D. Nath, University of Massachusetts Medical School
  • Gyongyi Szabo, University of Massachusetts Medical School
UMMS Affiliation
Department of Medicine, Division of Gastroenterology
Publication Date
4-24-2009
Document Type
Article
Subjects
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
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.
DOI of Published Version
10.1055/s-0029-1214372
Source
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
PubMed ID
19387916
Citation Information
Bharath D. Nath and Gyongyi Szabo. "Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells: implications for immunity" Vol. 29 Iss. 2 (2009) ISSN: 0272-8087 (Linking)
Available at: http://works.bepress.com/gyongyi_szabo/68/