Transcriptional regulation of mouse cyclooxygenase-2 gene by group-i phospholipase A2 in MC3T3 cells

Cyclooxygenase is a key enzyme in the biosynthesis of prostaglandins, the potent lipid mediators of inflammation. Two isoforms of this enzyme. cydooxygenase-1 and -2 (COX-1 and COX-2) have been identified. COX 1 is cunstitutiveiy expressed, while COX-2 is inducible by many cytokines, hormones and tumor promoters. Interestingly, COX-2 is also induced by group 1 phohpholipase A2 (PLA2-I) via its specific receptor in MC3T3-E1 cplls (Tohkin, M. et al., J. Biol. Chem. 268:2865. 1993). That, COX-2 is stimulated by PLA2-I is further attested by the facts that cells treated with PLA2-I increases COX-2 mRNA as well as prostaglandin E2 release. To fur thrr elucidate the transcriptional regulation of COX-2 gene by PLA2-I the promoter region of COX-2 was analyzed by deletion analysis. The promoter sequence ( -188 to -133 base pair) in the 5'flanking region of COX-2 gene, containing AP2 and XF-IL6 sites, appears to be essential for COX-2 induction by PLA2-I. Klecliophoretic mobility shift assay suggested that NF IL6. but not AP2, is involved in the PLA2-I-dependent transcriptional regulation of COX 2 gene These results raise (he possibility that the binding of PLA2 I to its receptor may lead to the activation of XF-IL6 which in turn induces COX 2 gene expression.