TNFα-Dependent Induction of Cyclooxygenase-2 Mediated by NFκB and NF-IL6

Abstract

MC3T3-E1 cell is an osteogenic line established from newborn mouse calvaria by Kodama and others.¹ Our laboratory has demonstrated that the cells release prostaglandin (PG) E2 into the culture medium as an essentially sole arachionate metabolite, and the PGE2 production is stimulated markedly by the addition of EGF, TGFβ, epinephrine or various PGs.^2–5 Several lines of evidence suggested that the increased PGE2 synthesis was attributed to the induction of cyclooxygenase enzyme by these compounds. Furthermore, we reported that the increased cyclooxygenase activity by PGs (PGF2α, PGE2, PGE1 and iloprost) was mostly attributed to the induction of cyclooxygenase-2 rather than cyclooxygenase-1.⁶ The quantification of c AMP and IP3 and the examination of the effects of various protein kinase inhibitors indicated that iloprost and PGE1 induced cyclooxygenase-2 through a pathway mediated by cAMP and A kinase. On the other hand, PGF2α induced cyclooxygenase-2 via PI turnover and protein kinase C. PGE2 was probably coupled with two or more pathways.