Control of cyclooxygenase-2 transcriptional activation by pro-inflammatory mediators

Cyclooxygenase-2 (COX-2) plays a key role in diverse inflammatory conditions. Its cellular levels depend on transcriptional activation by pro-inflammatory mediators. The mechanism by which phorbol esters and cytokines activate COX-2 gene expression has been extensively characterized. Several endogenous molecules and natural products have been reported to inhibit COX-2 expression by targeting at the transcriptional activation induced by pro-inflammatory mediators. This review highlights the importance of C/EBPbeta and NF-kappaB in COX-2 transcriptional activation by proinflammatory mediators and as targets of inhibition by endogenous molecules such as melatonin and natural products including salicylate and polyphenols. (C) 2004 Elsevier Ltd. All rights reserved.