Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease

Courtney S. Schaffert, Michael J. Duryee, Carlos D. Hunter, Bartlett C. Hamilton, Amy L. DeVeney, Mary M. Hueter, Lynell Warren Klassen, Geoffrey Milton Thiele

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflammation and fibrosis, and play a role in the development and/or progression of ALD.

Original languageEnglish (US)
Pages (from-to)1209-1218
Number of pages10
JournalWorld Journal of Gastroenterology
Volume15
Issue number10
DOIs
StatePublished - Mar 14 2009

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Keywords

  • Alcoholic liver disease
  • Fibrosis
  • Hepatocyte
  • Inflammation
  • Kupffer cells
  • Precision cut liver slices
  • Sinusoidal liver endothelial cells
  • Stellate cells

ASJC Scopus subject areas

  • Gastroenterology

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