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.
Takai
Shinji
S
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, and Department of Clinical Laboratory, National Hospital for Geriatric Medicine, Aichi, Japan.
Tokuda
Haruhiko
H
Hanai
Yoshiteru
Y
Kozawa
Osamu
O
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020928:Mitogen-Activated Protein Kinases; D020123:Sirolimus