Schaffert CS, Duryee MJ, Hunter CD, 3rd BCH, DeVeney AL, Huerter MM, Klassen LW, Thiele GM. Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease. World J Gastroenterol 2009; 15(10): 1209-1218 [PMID: 19291821 DOI: 10.3748/wjg.15.1209]
Corresponding Author of This Article
Michael J Duryee, Omaha Veterans Administration Medical Center, Research Service 151, Rm 321, 4101 Woolworth Avenue, Omaha, NE 68105, United States. mduryee@unmc.edu
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World J Gastroenterol. Mar 14, 2009; 15(10): 1209-1218 Published online Mar 14, 2009. doi: 10.3748/wjg.15.1209
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 3rd, Amy L DeVeney, Mary M Huerter, Lynell W Klassen, Geoffrey M Thiele
Courtney S Schaffert, Michael J Duryee, Carlos D Hunter, Bartlett C Hamilton 3rd, Amy L DeVeney, Mary M Huerter, Lynell W Klassen, Geoffrey M Thiele, Department of Internal Medicine, University of Nebraska Medical Center, 986350 Nebraska Medical Center, Omaha, NE 68198-6350, United States; Veterans Administration Alcohol Research Center, Omaha Veterans Administration Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States
Geoffrey M Thiele, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, United States
Author contributions: Schaffert CS, Duryee MJ, Hunter CD, Hamilton BC 3rd, DeVeney AL, Huerter MM, Klassen LW, Thiele GM contributed equally to the writing and preparation of this manuscript.
Correspondence to: Michael J Duryee, Omaha Veterans Administration Medical Center, Research Service 151, Rm 321, 4101 Woolworth Avenue, Omaha, NE 68105, United States. mduryee@unmc.edu
Telephone: +1-402-9953429
Fax: +1-402-449060
Received: December 17, 2008 Revised: January 17, 2009 Accepted: January 24, 2009 Published online: March 14, 2009
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.
