Alcohol-induced expression of the CD14 endotoxin receptor protein in rat Kupffer cells.
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.
Järveläinen
H A
HA
Alcohol Research Center, National Public Health Institute, Helsinki, Finland.
Oinonen
T
T
Lindros
K O
KO
D000209:Acute-Phase Proteins; D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000235:genetics*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D000431:Ethanol; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000099231:Lipopolysaccharide-Binding Protein; C048071:endotoxin receptor