MITOGEN-INDUCIBLE PROSTAGLANDIN-G H SYNTHASE IS EXPRESSED IN CANINE MASTOCYTOMA-CELLS/

A mitogen-inducible prostaglandin G/H synthase (PGHS-2 or cyclooxygena se-2) has recently been cloned from chicken and mouse fibroblasts. Thi s protein is distinct from classic prostaglandin G/H synthase (PGHS-1 or cyclooxygenase-1) but has a similar enzymatic activity. Because PGH S-1 is a rate-limiting enzyme in the synthesis of prostaglandins, PGHS -2 may also play an important role in prostaglandin production. To exa mine whether PGHS-2 is induced by phorbol ester in mast cells, we stud ied 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 maxim al induction after 4 h of incubation with 10 nM PMA. There was concent ration-dependent production of PGD2 after incubation with PMA. In cont rast, PGHS-1 mRNA was expressed in resting cells, and the expression o f PGHS-1 mRNA was down-regulated by PMA. Dexamethasone inhibited PMA-i nduced mRNA expression of PGHS-2 and PGD2 production. Aspirin had no e ffect on mRNA expression of PGHS-2 but inhibited PGD2 production. In c onclusion, PGHS-2 is induced by phorbol ester in canine mast cells. We speculate that PGHS-2 may be important in airway inflammation in whic h mast cells are activated.