Alcohol metabolites and lipopolysaccharide: roles in the development and/or progression of alcoholic liver disease.
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.
Schaffert
Courtney S
CS
Department of Internal Medicine, University of Nebraska Medical Center, 986350 Nebraska Medical Center, Omaha, NE 68198-6350, United States.
Duryee
Michael J
MJ
Hunter
Carlos D
CD
Hamilton
Bartlett C
BC
DeVeney
Amy L
AL
Huerter
Mary M
MM
Klassen
Lynell W
LW
Thiele
Geoffrey M
GM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003474:Curcumin / Q000627:therapeutic use; D018450:Disease Progression; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D000431:Ethanol; D003474:Curcumin