Drug inhibition and cellular regulation of prostaglandin G/H synthase isoenzyme 2.

Abstract

Prostaglandin G/H synthase isoenzyme 2 (PGHS-2) was identified as an immediate-early gene product induced by Rous sarcoma virus, serum, phorbol ester and a wide variety of other mitogens. Induction of PGHS-2 occurs through an increase in PGHS-2 gene transcription. Dexamethasone inhibits both the basal and induced levels of PGHS-2 mRNA. In contrast, PGHS-1 gene transcription rate, mRNA, and protein levels are unaffected by mitogens and dexamethasone. Post-transcriptional down-regulation of PGHS-2 mRNA plays a significant role in causing dexamethasone's effect. Specific cell systems have been identified which allow selective analysis of PGHS-1 and PGHS-2 at the nucleic acid and protein levels. These cell systems indicate that PGHS-1 and PGHS-2 may have different sensitivities to non-steroidal anti-inflammatory drugs. Furthermore, inhibition of PGHS activity correlates well with suppression of the transformed phenotype in an in vitro cell model.