Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene.
Glucocorticoids block the induced secretion of prostaglandins in a variety of biological contexts. We have identified a primary response gene, TIS10, which encodes a mitogen-inducible prostaglandin synthase/cyclooxygenase in Swiss 3T3 cells. TIS10 is distinct from prostaglandin synthase/cyclooxygenase. (EC 1.14.99.1), previously cloned from mouse, man, and sheep. Dexamethasone blocks prostaglandin E2 synthesis by 3T3 cells in response to tetradecanoylphorbol acetate. Dexamethasone also blocks both phorbol ester- and forskolin-induced TIS10 mRNA accumulation. In contrast, phorbol esters, forskolin, and dexamethasone have little or no effect on the levels of prostaglandin synthase/cyclooxygenase mRNA in 3T3 cells. Moreover, dexamethasone does not inhibit induction of TIS8/egr-1, another primary response gene. Inhibition of the synthesis of TIS10 prostaglandin synthase/cyclooxygenase may be a principal mechanism by which glucocorticoids block prostaglandin synthesis and secretion.
Kujubu
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DA
Department of Medicine, UCLA School of Medicine 90024.
Herschman
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HR
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D051379:Mice; D008934:Mitogens; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008934:Mitogens; D012333:RNA, Messenger; D005576:Colforsin; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate