SECRETION OF PROSTAGLANDINS ELICITED BY LIPOPOLYSACCHARIDE AND ETHANOL IN CULTURED RAT KUPFFER CELLS

Prostaglandins (PGs) released by cultured rat Kupffer cells in respons e to stimulation with lipopolysaccharide (LPS) or ethanol were extract ed from culture media, separated by HPLC and measured by radioimmunoas say. LPS (0.5-5 mu g/ml) enhanced. after a 3-4 hrs lag period. the pro duction of PGE2 (7-10 fold by 24 hrs), thromboxane B2 (2-3 fold) and P GD2, PG 6-keto-F1 alpha. PGF2 alpha(20-50% each): This effect was not inhibited by 30 mu M aspirin but was reduced by dexamethasone. Ethanol (25-85 mM) gradually increased the release of PGE2 (40-90% by 24 hrs) and other PGs (10-30%), with 30 mu M aspirin eliminating this effect. When added together with LPS, ethanol potentiated the endotoxin actio n. We suggest that LPS causes synthesis of the inducible cyclooxygenas e-2 form in Kupffer cells, whereas ethanol exerts its effect via the p reexisting cyclooxygenase-1 mainly by increasing the free arachidonic acid content. (C) 1995 Academic Press, Inc.