Limitation by p70 S6 kinase of platelet-derived growth factor-BB–induced interleukin 6 synthesis in osteoblast-like MC3T3-E1 cells

It has been reported that platelet-derived growth factor–BB (PDGF-BB) stimulates interleukin 6 (IL-6) in osteoblasts. In the present study, we investigated the mechanism of IL-6 synthesis induced by PDGF-BB in osteoblast-like MC3T3-E1 cells. Platelet-derived growth factor–BB time-dependently induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p70 S6 kinase. PD98059 (an inhibitor of MAP kinase/extracellular signal-regulated kinase kinase [MEK]), SB203580 (an inhibitor of p38 MAP kinase), or SP600125 (an inhibitor of SAPK/JNK) suppressed the IL-6 synthesis induced by PDGF-BB. Rapamycin, an inhibitor of p70 S6 kinase, significantly enhanced the PDGF-BB–stimulated IL-6 synthesis. The PDGF-BB–induced phosphorylation of p70 S6 kinase was suppressed by rapamycin. Rapamycin failed to affect the PDGF-BB–induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or SAPK/JNK. These results strongly suggest that PDGF-BB stimulates IL-6 synthesis through activation of 3 MAP kinases in osteoblasts and that p70 S6 kinase negatively regulates the IL-6 synthesis.