Differential inhibition of prostaglandin and superoxide production by dexamethasone in primary cultures of rat Kupffer cells.
Dexamethasone inhibited the stimulus-induced prostaglandin E2 formation by rat Kupffer cells in primary culture, e.g. after treatment with zymosan, phorbol ester, calcium ionophore A23187, platelet-activating factor or lipopolysaccharide. Prostaglandin E2 production from added free arachidonic acid was not influenced by the hormone. The time course, as well as the partial inhibition of the hormone effect by actinomycin D and cycloheximide, point to the hormone-induced formation of a protein which regulates phospholipase A2. The hormone did not affect the phagocytotic activity of the Kupffer cells. The quantity of [3H]arachidonic acid incorporated into phospholipids was also not altered by dexamethasone. After stimulation with zymosan, [3H]arachidonic acid was liberated from phosphatidylcholine only. Superoxide generation by rat Kupffer cells was induced by zymosan, phorbol ester and, to a much smaller extent, by platelet-activating factor. A23187 and lipopolysaccharide were without effect. In contrast to prostaglandin formation, the generation of superoxide was not influenced by dexamethasone. These results indicate that in cultured rat Kupffer cells prostaglandin formation and superoxide generation are independently triggered processes.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D013481:Superoxides; D016718:Arachidonic Acid; D003907:Dexamethasone; D015232:Dinoprostone