Premium
Zinc suppresses IL‐6 synthesis by prostaglandin F 2α in osteoblasts: Inhibition of phospholipase C and phospholipase D
Author(s) -
Hatakeyama Daijiro,
Kozawa Osamu,
Otsuka Takanobu,
Shibata Toshiyuki,
Uematsu Toshihiko
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10166
Subject(s) - phospholipase c , protein kinase c , phospholipase d , chemistry , activator (genetics) , pld2 , protein kinase a , biochemistry , kinase , signal transduction , microbiology and biotechnology , biology , phosphatidylcholine , receptor , phospholipid , membrane
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.