Tiludronate inhibits interleukin-6 synthesis in osteoblasts: Inhibition of phospholipase D activation in MC3T3-E1 cells

被引:0
作者
Tokuda, H [1 ]
Kozawa, O
Harada, A
Uematsu, T
机构
[1] Chubu Natl Hosp, Dept Internal Med, Natl Inst Longev Sci, Aichi 474, Japan
[2] Chubu Natl Hosp, Dept Orthoped Surg, Natl Inst Longev Sci, Aichi 474, Japan
[3] Gifu Univ, Sch Med, Dept Pharmacol, Gifu 500, Japan
关键词
bisphosphonate; prostaglandin F-2 alpha; interleukin-6; phospholipase D; osteoblast;
D O I
10.1002/(SICI)1097-4644(19980601)69:3<252::AID-JCB3>3.0.CO;2-Q
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In previous studies, we have reported that PGF(2 alpha) stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein in osteoblast-like MC3T3-E1 cells, and that PGF(2 alpha) and PGE(1) induce interleukin-6 (IL-6) synthesis via activation of protein kinase C and protein kinase A, respectively. In the present study, we investigated the effect of tiludronate, a bisphosphonate known to inhibit bone resorption, on the PGF(2 alpha)-and PGE(1)-induced IL-6 synthesis in these cells. Tiludronate significantly suppressed the PGF(2 alpha)-induced IL-6 secretion in a dose-dependent manner in the range between 0.1 and 30 mu M. However, the IL-6 secretion induced by PGE(1) or (Bu)(2)cAMP was hardly affected by tiludronate. The choline formation induced by PGF(2 alpha) was reduced by tiludronate dose-dependently in the range between 0.1 and 30 mu M. On the contrary, tiludronate had no effect on PGF(2 alpha)-induced formation of inositol phosphates. Tiludronate suppressed the choline formation induced by NaF, known as an activator of heterotrimeric CTP-binding protein. However, tiludronate had little effect on the formation of choline induced by TPA, a protein kinase C activator. Tiludronate significantly inhibited the NaF-induced IL-6 secretion in human osteoblastic osteosarcoma Saos-2 cells. These results strongly suggest that tiludronate inhibits PGF(2 alpha)-induced IL-6 synthesis via suppression of phosphatidylcholine-hydrolyzing phospholipase D activation in osteoblasts, and that the inhibitory effect is exerted at the point between heterotrimeric GTP-binding protein and phospholipase D. (C) 1998 Wiley-Liss, Inc.
引用
收藏
页码:252 / 259
页数:8
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