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Semin Liver Dis 2009; 29(2): 166-177
DOI: 10.1055/s-0029-1214372
© Thieme Medical Publishers

Alcohol-induced Modulation of Signaling Pathways in Liver Parenchymal and Nonparenchymal Cells: Implications for Immunity

Bharath Nath1 , Gyongyi Szabo1
  • 1Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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Publication History

Publication Date:
22 April 2009 (online)

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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-α 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.

KEYWORDS

Ethanol - steatosis - inflammation - toll-like receptors - hepatitis

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Gyongyi SzaboM.D. Ph.D. 

Director of Hepatology and Liver Center, Department of Medicine, University of Massachusetts Medical School

364 Plantation Street, LRB 215, Worcester, MA 01605

Email: Gyongyi.Szabo@umassmed.edu

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