A PPAR-independent pathway to PUFA-induced COX-2 expression

Derecka, K and Sheldrick, E L and Wathes, D C and Abayasekara, D R E and Flint, A P F (2008) A PPAR-independent pathway to PUFA-induced COX-2 expression. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 287 (1-2). pp. 65-71.

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Polyunsaturated fatty acids (PUFAs) induce COX-2 in bovine endometrial stromal cells through activation of peroxisome-proliferator-activated receptor alpha (PPAR alpha). We have investigated alternative (PPAR-independent) pathways to COX-2 induction using a reporter construct driven by a COX-2 gene promoter sequence lacking a PPAR response element. This construct was induced by PUFAs, but not by PPAR agonists. PPAR-independent reporter gene expression occurred 6 h after PPAR-dependent induction of the endogenous COX-2 gene. In contrast to PPAR-dependent COX-2 induction, which is not affected by NF-kappa B inhibitors, the PPAR-independent pathway was blocked by the NF-kappa B inhibitor MG132 or following deletion of NF-kappa B sites in the COX-2 promoter. The PPAR-independent effect of PUFA was mimicked by the PKC activators 4 beta-PMA and prostaglandin F-2 alpha, but was not blocked by the PKC inhibitor RO318425. The results demonstrate a pathway to the induction of COX-2 by PUFAs requiring NF-kappa B but not PPAR or PKC. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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