Activation of Cytosolic Phospholipase A2 by Platelet-derived Growth Factor Is Essential for Cyclooxygenase-2-dependent Prostaglandin E2 Synthesis in Mouse Osteoblasts Cultured with Interleukin-1

• Published in: The Journal of biological chemistry 1997-02, Vol.272 (9), p.5952-5958
• Main Authors: Chen, Qing-Rong, Miyaura, Chisato, Higashi, Sayumi, Murakami, Makoto, Kudo, Ichiro, Saito, Shigeru, Hiraide, Takatoshi, Shibasaki, Yoshinobu, Suda, Tatsuo
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic Acid - pharmacology; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - biosynthesis; Enzyme Induction; Interleukin-1 - pharmacology; Isoenzymes - metabolism; Mice; Mice, Inbred C57BL; Osteoblasts - metabolism; Phospholipases A - metabolism; Phospholipases A2; Platelet-Derived Growth Factor - metabolism; Prostaglandin-Endoperoxide Synthases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.9.5952

The synthesis of prostaglandins (PGs) is regulated by the arachidonic acid release by phospholipase A2 (PLA2) and its conversion to PGs by cyclooxygenase (COX). In the present study, we examined the regulation of PG synthesis by interleukin (IL)-1α in primary mouse osteoblastic cells isolated from mouse calvaria. Although IL-1α greatly enhanced cox-2 mRNA expression and its protein levels, PGE2 was not produced until 24 h. When arachidonic acid was added to osteoblastic cells precultured with IL-1α for 24 h, PGE2 was produced within 10 min. Of several growth factors tested, platelet-derived growth factor (PDGF) specifically initiated the rapid synthesis of PGE2, which was markedly suppressed by a selective inhibitor of cox-2 (NS-398). In mouse osteoblastic cells, cytosolic PLA2 (cPLA2) mRNA and its protein were constitutively expressed and increased approximately 2-fold by IL-1α, but secretory PLA2 mRNA was not detected. PDGF rapidly stimulated PLA2 activity, which was blocked completely by a cPLA2 inhibitor (arachidonyltrifluoromethyl ketone). The PDGF-induced cPLA2 activation was accompanied by phosphorylation of its protein. These results indicate that cox-2 induction by IL-1α is not sufficient, but cPLA2 activation by PDGF is crucial for IL-1α-induced PGE2 synthesis in mouse osteoblasts.