Zinc suppresses IL-6 synthesis by prostaglandin F2α in osteoblasts: Inhibition of phospholipase C and phospholipase D

✍ Scribed by Daijiro Hatakeyama; Osamu Kozawa; Takanobu Otsuka; Toshiyuki Shibata; Toshihiko Uematsu

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 167 KB
• Volume: 85
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10166

✦ Synopsis

Abstract

We previously reported that prostaglandin F~2α~ (PGF~2α~) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP‐binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast‐like MC3T3‐E1 cells and that PGF~2α~ stimulates the synthesis of interleukin‐6 (IL‐6) via PKC‐dependent p44/p42 mitogen‐activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF~2α~‐induced IL‐6 synthesis in these cells. Zinc complex of l‐carnosine (l‐CAZ) dose‐dependently suppressed the PGF~2α~‐stimulated IL‐6 synthesis. In addition, zinc alone reduced the IL‐6 synthesis. L‐CAZ suppressed the PGF~2α~‐induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP‐binding protein, was not affected by l‐CAZ. l‐CAZ reduced the PGF~2α~‐stimulated formation of inositol phosphates and choline. However, l‐CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF~2α~‐induced IL‐6 synthesis via suppression of phosphoinositide‐hydrolyzing phospholipase C and phosphatidylcholine‐hydrolyzing phospholipase D in osteoblasts. J. Cell. Biochem. 85: 621–628, 2002. © 2002 Wiley‐Liss, Inc.