ALCOHOL-INDUCED EXPRESSION OF THE CD14 ENDOTOXIN RECEPTOR PROTEIN IN RAT KUPFFER CELLS

Gut-derived endotoxins (lipopolysaccharide, LPS) are believed to contr ibute to alcohol-induced liver disease (ALD) by stimulating Kupffer ce lls, the resident liver macrophages, to release proinflammatory cytoki nes. This activation is largely mediated by CD14, a high-affinity memb rane-anchored receptor for LPS. We observed, by chemiluminescence-enha nced detection, an increase in immunoreactive CD14 protein in Kupffer cells isolated from rats treated with ethanol for 2 weeks. Immunocytof luorescence experiments confirmed that this increase was confined to t he membranes of Kupffer cells from the alcohol-treated rats. The incre ase was regulated pretranslationally: a 3-fold elevation (p < 0.01) in the hepatic revel of CD14 mRNA was observed. The marked increase in C D14 expression suggests a new mechanism by which alcohol increases the LPS-mediated cytokine signaling by the liver macrophages, thus promot ing the interaction between alcohol and endotoxins in the development of liver damage.