Prostaglandin E sub(2) amplifies cytosolic phospholipase A sub(2)- and cyclooxygenase-2-dependent delayed prostaglandin E sub(2) generation in mouse osteoblastic cells. Enhancement by secretory phospholipase A sub(2)

• Published in: The Journal of biological chemistry 1997-08, Vol.272 (32), p.19891-19897
• Main Authors: Murakami, M, Kuwata, H, Amakasu, Y, Shimbara, S, Nakatani, Y, Atsumi, G-I, Kudo, I
• Format: Article
• Language: English
• ISSN: 0021-9258

We used the MC3T3-E1 cell line, which originates from C57BL/6J mouse that is genetically type IIA secretory phospholipase A sub(2) (sPLA sub(2))-deficient, to reveal the type IIA sPLA sub(2)-independent route of the prostanglandin (PG) biosynthetic pathway. Kinetic and pharmacological studies showed that delayed PGE sub(2) generation by this cell line in response to interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF alpha ) was dependent upon cytosolic phospholipase A sub(2) (cPLA sub(2)) and cyclooxygenase (COX)-2. Expression of these two enzymes was reduced by cPLA sub(2) or COX-2 inhibitors and restored by adding exogenous arachidonic acid or PGE sub(2), indicating that PGE sub(2) produced by these cells acted as an autocrine amplifier of delayed PGE sub(2) generation through enhanced cPLA sub(2) and COX-2 expression. Exogenous addition or enforced expression of type IIA sPLA sub(2) significantly increased IL-1 beta /TNF alpha -initiated PGE sub(2) generation, which was accompanied by increased expression of both cPLA sub(2) and COX-2 and suppressed by inhibitors of these enzymes. Thus, our results revealed a particular cross-talk between the two PLA sub(2) enzymes and COX-2 for delayed PGE sub(2) biosynthesis by a type IIA sPLA sub(2)-deficient cell line. cPLA sub(2) is responsible for initiating COX-2-dependent delayed PGE sub(2) generation, and sPLA sub(2), if introduced, enhances PGE sub(2) generation by increasing cPLA sub(2) and COX-2 expression via endogenous PGE sub(2).