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

✍ Scribed by Yoshiteru Hanai; Haruhiko Tokuda; Toshiki Ohta; Rie Matsushima-Nishiwaki; Shinji Takai; Osamu Kozawa

• Book ID: 102304584
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 191 KB
• Volume: 99
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21007

✦ Synopsis

Abstract

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‐3β. Akt inhibitor, 1L‐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‐3β 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‐3β. 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. © 2006 Wiley‐Liss, Inc.