Phosphatidylinositol 3-kinase/akt auto-regulates PDGF-BB-stimulated interleukin-6 synthesis in osteoblasts

被引:12
作者
Hanai, Yoshiteru
Tokuda, Haruhiko
Ohta, Toshiki
Matsushima-Nishiwaki, Rie
Takai, Shinji
Kozawa, Osamu
机构
[1] Gifu Univ, Sch Med, Dept Pharmacol, Gifu 5011194, Japan
[2] Natl Hosp Geriatr Med, Natl Ctr Geriatr & Gerontol, Dept Internal Med, Aichi 4748511, Japan
[3] Natl Hosp Geriatr Med, Natl Ctr Geriatr & Gerontol, Dept Clin Lab, Aichi 4748511, Japan
关键词
platelet-derived growth factor (PDGF); interleukin-6 (IL-6); phosphatidylinositol; 3-kinase; Akt; osteoblast;
D O I
10.1002/jcb.21007
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
It has been reported that platelet-derived growth factor (PDGF)-BB stimulates the synthesis of interleukin (IL)-6 in osteoblasts. In the present study, we investigated whether the phosphatidylinositol 3-kinase (PI3K)/Akt is involved in the PDGF-BB-induced IL-6 synthesis in osteoblast-like MC3T3-E1 cells. PDGF-BB markedly induced the phosphorylation of Akt and GSK-3 beta. Akt inhibitor, 1(L)-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, significantly amplified the synthesis of IL-6 by PDGF-BB. The PDGF-BB-induced GSK-3p phosphorylation was suppressed by the Akt inhibitor. The IL-6 synthesis stimulated by PDGF-BB was markedly enhanced by LY294002 and wortmannin, inhibitors of PI3K. Wortmannin and LY294002 suppressed the PDGF-BB-induced phosphorylation of Akt and GSK-3 beta. Taken together, these results strongly suggest that PI3K/Akt negatively regulates the PDGF-BB-stimulated IL-6 synthesis in osteoblasts. J. Cell. Biochem. 99:1564-1571, 2006. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:1564 / 1571
页数:8
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