Cytokines and the molecular mechanisms of alcoholic liver disease.

Journal Article

This manuscript was given as a plenary lecture at the annual meeting of the Research Society on Alcoholism in July of 1999. It describes the general mechanisms by which tumor necrosis factor (TNF) alpha, an injury-related cytokine, promotes liver regeneration and then details how TNF-initiated hepatotrophic signals are inhibited by chronic ethanol consumption. There is evidence that chronic ethanol exposure impairs the TNF-dependent activation of stress-activated protein kinases and some of their targets, including the growth-stimulatory DNA binding protein, c-Jun. Ethanol exposure also prevents TNF from activating the redox-sensitive transcription factor, NF kappa B, in regenerating hepatocytes. These effects are followed by decreased hepatocyte proliferation, as well as by impaired induction of TNF-regulated survival factors, such as Bcl-xL, in the liver. Thus, chronic ethanol consumption may damage the liver by inhibiting the hepatotrophic and hepatoprotective actions of TNFalpha and other growth-regulatory cytokines.

Full Text

Duke Authors

Cited Authors

  • Diehl, AM

Published Date

  • September 1999

Published In

Volume / Issue

  • 23 / 9

Start / End Page

  • 1419 - 1424

PubMed ID

  • 10512305

International Standard Serial Number (ISSN)

  • 0145-6008


  • eng

Conference Location

  • England