Anti-inflammatory glucocorticoid action: inhibition of griPGHS, a new cyclooxygenase.

Abstract

Our understanding of the anti-inflammatory actions of glucocorticoid hormones has significantly advanced in the past year with the discovery of a second cyclooxygenase gene which we call 'glucocorticoid-regulated inflammatory prostaglandin G/H synthase' (griPGHS). In mouse fibroblasts and human monocytes levels of griPGHS mRNA and protein rise dramatically in response to growth factors, cytokines, and oncogene activation. These inductions are markedly suppressed by the glucocorticoid hormone, dexamethasone. This stands in contrast to the behavior of the previously cloned cyclooxygenase (PGHS), which appears to be constitutively expressed. Thus far, data show that griPGHS is increased in many other systems where prostaglandin biosynthesis is regulated, including models of inflammation, tissue injury, and hormonal control of reproductive processes. Thus, griPGHS is likely to be a key mediator of many clinically relevant processes and as such represents an important target for both steroidal and nonsteroidal anti-inflammatory agents.