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Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin
N Enomoto1, K Ikejima, S Yamashina
1Department of Gastroenterology, Juntendo University, Bunkyo-ku, Tokyo, Japan.
Alcoholism, Clinical and Experimental Research
|June 19, 2001
Summary
Alcohol increases gut permeability, leading to higher endotoxin levels and sensitized Kupffer cells. This sensitization to lipopolysaccharide (LPS) contributes to alcohol-induced liver injury.
Area of Science:
- Hepatology
- Immunology
- Gastroenterology
Background:
- Alcohol-induced liver injury involves endotoxin and Kupffer cells.
- Ethanol exposure sensitizes Kupffer cells to endotoxin.
- A novel animal model of ethanol hepatotoxicity was established based on Kupffer cell sensitization.
Purpose of the Study:
- To elucidate the mechanisms by which alcohol sensitizes Kupffer cells to lipopolysaccharide (LPS).
Main Methods:
- Rats received ethanol intragastrically; ethanol levels, elimination, and portal vein endotoxin were measured.
- Gut permeability was assessed using horseradish peroxidase translocation.
- Kupffer cells were isolated, and LPS-induced intracellular calcium and TNF-alpha production were measured; CD14 expression was evaluated.
Main Results:
- Ethanol treatment increased gut permeability and portal vein endotoxin levels.
- Isolated Kupffer cells from ethanol-treated rats showed increased CD14 expression, intracellular calcium response, and TNF-alpha production upon LPS stimulation.
- Antibiotic treatment prevented the increase in portal vein endotoxin and blocked Kupffer cell sensitization.
Conclusions:
- Ethanol-treated rats exhibit Kupffer cell sensitization to LPS.
- Increased gut permeability is a key factor in alcohol-induced liver injury.