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

• Published in: Molecular and cellular endocrinology Vol. 287; no. 1; pp. 65 - 71
• Main Authors: Derecka, K., Sheldrick, E.L., Wathes, D.C., Abayasekara, D.R.E., Flint, A.P.F.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 11-06-2008; Elsevier
• Subjects: Animals; Arachidonic acid; Arachidonic Acid - pharmacology; Base Sequence; Bovine endometrium; Cattle; Cells, Cultured; Chloramphenicol O-Acetyltransferase - metabolism; Cyclooxygenase 2; Cyclooxygenase 2 - biosynthesis; Enzyme Induction - drug effects; Fatty Acids, Unsaturated - metabolism; Fatty Acids, Unsaturated - pharmacology; Models, Biological; Molecular Sequence Data; NF-kappa B - metabolism; Peroxisome Proliferator-Activated Receptors - metabolism; Peroxisome-proliferator-activated receptor; Promoter Regions, Genetic - genetics; Protein kinase C; Protein Kinase C - metabolism; Stromal Cells - drug effects; Stromal Cells - enzymology; Time Factors; Transfection; Protein kinase C; Peroxisome-proliferator-activated receptor; Arachidonic acid; Cyclooxygenase 2; Bovine endometrium; Life Sciences
• ISSN: 0303-7207; 1872-8057; 0303-7207
• DOI: 10.1016/j.mce.2008.02.015

Polyunsaturated fatty acids (PUFAs) induce COX-2 in bovine endometrial stromal cells through activation of peroxisome-proliferator-activated receptor alpha (PPARα). 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-κB inhibitors, the PPAR-independent pathway was blocked by the NF-κB inhibitor MG132 or following deletion of NF-κB sites in the
COX-2 promoter. The PPAR-independent effect of PUFA was mimicked by the PKC activators 4β-PMA and prostaglandin F
2α, but was not blocked by the PKC inhibitor RO318425. The results demonstrate a pathway to the induction of COX-2 by PUFAs requiring NF-κB but not PPAR or PKC.