Diverse effects of ethanol on the pathway of inducible prostaglandin E 2 production in macrophages

Abstract

The effects of ethanol on inducible prostaglandin production in RAW macrophages were investigated. Indomethacin (1 μM) or cycloheximide (1 μM) abolished prostaglandin E2 (PGE 2) production induced by lipopolysaccharide (LPS, 1 μg/ml). Ethanol at concentrations from 100 mM to 600 mM concentration-dependently inhibited inducible PGE 2 production, while ethanol only at higher concentrations (400 mM or more) showed cytotoxity to the cells. Cyclooxygenase-2 (COX-2) activity, estimated by transformation of exogenous arachidonic acid into PGE 2, was not affected by ethanol (100–400 mM). LPS-induced expression of COX-2 mRNA was inhibited by ethanol (50–400 mM). On the other hand, protein expression of COX-2 by LPS was significantly increased by ethanol (100–400 mM). Ethanol alone at concentrations up to 600 mM did not induce expression of COX-2 protein. In a medium containing arachidonic acid (1 μM), ethanol at a low concentration (100 mM) did not significantly affect LPS-induced PGE 2 production. These results suggest that ethanol shows diverse effects on the pathway of inducible PGE 2 production in macrophages. Finally, ethanol may suppress utilization of arachidonic acid, resulting in reduction of inducible PGE 2 production. Further study is needed to elucidate the mechanism of dissociation of ethanol effects on protein and mRNA expression.