Alcohol-Induced Expression of the CD14 Endotoxin Receptor Protein in Rat Kupffer Cells |
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Authors: | Harri A Järveläinen Teija Oinonen Kai O Lindros |
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Institution: | Alcohol Research Center, National Public Health Institute, Helsinki, Finland. [recd]April 2, 1997 [rev]August 1, 1997 |
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Abstract: | Gut-derived endotoxins (lipopolysaccharide, LPS) are believed to contribute to alcohol-induced liver disease (ALD) by stimulating Kupffer cells, the resident liver macrophages, to release proinflammatory cytokines. This activation is largely mediated by CD14, a high-affinity membrane-anchored receptor for LPS. We observed, by chemiluminescence-enhanced detection, an increase in immunoreactive CD14 protein in Kupffer cells isolated from rats treated with ethanol for 2 weeks. Immunocytofluorescence experiments confirmed that this increase was confined to the membranes of Kupffer cells from the alcohol-treated rats. The increase was regulated pretranslationally: a 3-fold elevation ( p < 0.01) in the hepatic level of CD14 mRNA was observed. The marked increase in CD14 expression suggests a new mechanism by which alcohol increases the LPS-mediated cytokine signaling by the liver macrophages, thus promoting the interaction between alcohol and endotoxins in the development of liver damage. |
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Keywords: | Endotoxins Alcoholic Liver Disease Lipopolysaccharide CD14 Protein |
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