Mechanism of stimulation by human interferon of prostaglandin synthesis in human cell lines.
Human interferon beta (IFN-beta) stimulated the synthesis of prostaglandin E (PGE) and prostaglandin F2 alpha in IFN-sensitive RSa and GM258 cell lines, but not in IFN-resistant HEC-1 cells. IFN-beta at a concentration of 1000 units/ml elicited 2- to 3-fold increases in PGE production in these cell lines. In the presence of exogenous arachidonic acid (1 microgram/ml), IFN-pretreated cells produced 5-fold more PGE compared to the cell cultures in the absence of arachidonic acid. Prednisolone, an inhibitor of phospholipase A2, at a concentration of 2 micrograms/ml inhibited the enhanced synthesis of PGE by IFN-pretreated cells. Indomethacin (4 micrograms/ml), a potent fatty acid cyclooxygenase inhibitor, also inhibited the increased synthesis of PGE. IFN stimulated the release of [14C]arachidonic acid from phospholipids but did not stimulate the activity of fatty acid cyclooxygenase. These data suggest that IFN stimulates prostaglandin synthesis by promoting the release of arachidonic acid from phospholipids. Since cycloheximide and actinomycin D inhibited the stimulation of PGE synthesis, the stimulation of prostaglandin synthesis by IFN seemed to be due to de novo enzyme synthesis which catalyzes the release of fatty acid. Addition of exogenous PGE suppressed the growth of RSa and GM258 cells. Prednisolone and iodomethacin partially inhibited anti-cell growth activity of IFN, suggesting a possibility that IFN-inhibited cell growth was partly mediated by prostaglandin.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D015232:Dinoprostone; D005347:Fibroblasts; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D011239:Prednisolone / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D007372:Interferons; D011239:Prednisolone; D015232:Dinoprostone; D007213:Indomethacin