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

Bharath Nath, G. Szabó

Research output: Contribution to journalReview article

41 Citations (Scopus)

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 ethanolexposed 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.

Original languageEnglish
Pages (from-to)166-177
Number of pages12
JournalSeminars in Liver Disease
Volume29
Issue number2
DOIs
Publication statusPublished - May 2009

Fingerprint

Immunity
Alcohols
Ethanol
Liver
Lipids
Antiviral Agents
Hepatocytes
Wounds and Injuries
Toll-Like Receptor 4
Kupffer Cells
Adaptive Immunity
Fatty Liver
Autoimmunity
Innate Immunity
Endotoxins
Immune System
Necrosis
Tumor Necrosis Factor-alpha
Cytokines
Inflammation

Keywords

  • Ethanol
  • Hepatitis
  • Inflammation
  • Steatosis
  • Toll-like receptors

ASJC Scopus subject areas

  • Hepatology

Cite this

Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells : Implications for immunity. / Nath, Bharath; Szabó, G.

In: Seminars in Liver Disease, Vol. 29, No. 2, 05.2009, p. 166-177.

Research output: Contribution to journalReview article

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