Secretion of prostaglandins elicited by lipopolysaccharide and ethanol in cultured rat Kupffer cells.

Prostaglandins (PGs) released by cultured rat Kupffer cells in response to stimulation with lipopolysaccharide (LPS) or ethanol were extracted from culture media, separated by HPLC and measured by radioimmunoassay. LPS (0.5-5 micrograms/ml) enhanced, after a 3-4 hrs lag period, the production of PGE2 (7-10 fold by 24 hrs), thromboxane B2 (2-3 fold) and PGD2. PG 6-keto-F1 alpha, PGF2 alpha (20-50% each). This effect was not inhibited by 30 microM 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 microM aspirin eliminating this effect. When added together with LPS, ethanol potentiated the endotoxin action. We suggest that LPS causes synthesis of the inducible cyclooxygenase-2 form in Kupffer cells, whereas ethanol exerts its effect via the pre-existing cyclooxygenase-1 mainly by increasing the free arachidonic acid content.