Interferon inhibits prostaglandin biosynthesis in macrophages: effects on arachidonic acid metabolism.
Mouse resident peritoneal M phi produced considerable amounts of PGE when triggered in vitro with soluble or particulate stimuli. Preexposure of M phi to IFN-beta dramatically decreased PGE production. This effect depended on the dose of IFN-beta used and was abolished by anti-IFN-beta globulin. In addition to PGE, other AA metabolites of the cyclooxygenase pathway, namely TXB2 and 6-keto PGF1 alpha, were decreased in IFN-beta-treated M phi. However, IFN-beta did not have any effect on cyclooxygenase activity of M phi, indicating that an earlier step of PG biosynthesis was likely to be the target of its inhibitory action. Indeed, the release of radioactive compounds from M phi prelabeled with [14C]AA was strongly impaired by IFN-beta, suggesting that IFN-beta would decrease PG production in M phi by blocking phospholipase activation. The possibility that the IFN-beta effect on phospholipase could be mediated through the increase of the intracellular levels of cAMP is suggested.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010740:Phospholipases / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D007370:Interferon Type I; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D016718:Arachidonic Acid; D013928:Thromboxane A2; D003994:Bucladesine; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases