Mitogen-inducible prostaglandin G/H synthase is expressed in canine mastocytoma cells.
A mitogen-inducible prostaglandin G/H synthase (PGHS-2 or cyclooxygenase-2) has recently been cloned from chicken and mouse fibroblasts. This protein is distinct from classic prostaglandin G/H synthase (PGHS-1 or cyclooxygenase-1) but has a similar enzymatic activity. Because PGHS-1 is a rate-limiting enzyme in the synthesis of prostaglandins, PGHS-2 may also play an important role in prostaglandin production. To examine whether PGHS-2 is induced by phorbol ester in mast cells, we studied mRNA expression of PGHS-2 and also measured prostaglandin D2 (PGD2) production when canine mastocytoma cells were incubated with phorbol myristate acetate (PMA). PGHS-2 mRNA was induced by PMA, with a maximal induction after 4 h of incubation with 10 nM PMA. There was concentration-dependent production of PGD2 after incubation with PMA. In contrast, PGHS-1 mRNA was expressed in resting cells, and the expression of PGHS-1 mRNA was down-regulated by PMA. Dexamethasone inhibited PMA-induced mRNA expression of PGHS-2 and PGD2 production. Aspirin had no effect on mRNA expression of PGHS-2 but inhibited PGD2 production. In conclusion, PGHS-2 is induced by phorbol ester in canine mast cells. We speculate that PGHS-2 may be important in airway inflammation in which mast cells are activated.
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Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Levine
T M
TM
Lazarus
S C
SC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004285:Dogs; D015870:Gene Expression / Q000187:drug effects; D008407:Mast Cells / Q000201:enzymology*; D012515:Mast-Cell Sarcoma / Q000201:enzymology*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D015230:Prostaglandin D2