(-)-Epigallocatechin gallate inhibits basic fibroblast growth factor-stimulated interleukin-6 synthesis in osteoblasts.
We previously showed that basic fibroblast growth factor (FGF-2) activates the mitogen-activated protein (MAP) kinase superfamily in osteoblast-like MC3T3-E1 cells and that p38 MAP kinase functions as a positive regulator in the FGF-2-stimulated synthesis of interleukin-6 (IL-6), a potent bone-resorptive agent, in these cells. In the present study, we investigated the exact mechanism of IL-6 and the effects of (-)-epi-gallocatechin gallate (EGCG), one of the major green tea flavonoids, on the synthesis of IL-6. PD98059, an inhibitor of MEK, but not SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase, suppressed FGF-2-stimulated IL-6 synthesis. EGCG significantly reduced the IL-6 synthesis stimulated by FGF-2 in a dose-dependent manner. EGCG attenuated the FGF-2-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. These results strongly suggest that EGCG inhibits the FGF-2-stimulated synthesis of IL-6 at least partly via suppression of the p44/p42 MAP kinase pathway and the p38 MAP kinase pathway in osteoblasts.
Tokuda
H
H
Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan. tokuda@ncgg.go.jp
Takai
S
S
Hanai
Y
Y
Matsushima-Nishiwaki
R
R
Yamauchi
J
J
Harada
A
A
Hosoi
T
T
Ohta
T
T
Kozawa
O
O
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009930:Organic Chemicals / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000873:Anthracenes; D015850:Interleukin-6; D009930:Organic Chemicals; C466090:PD 98058; D016222:Fibroblast Growth Factor 2; C432165:pyrazolanthrone; D002392:Catechin; C045651:epigallocatechin gallate; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases