Involvement of p42/p44 MAP kinase in endothelin-1-induced interleukin-6 synthesis in osteoblast-like cells.
We previously reported that endothelin-1 induces synthesis of interleukin-6 (IL-6) via activation of protein kinase C in osteoblast-like MC3T3-E1 cells. In the present study, we further investigated whether p42/p44 mitogen-activated protein (MAP) kinase is involved in endothelin-1-induced IL-6 synthesis in these cells. Endothelin-1 stimulated p42/p44 MAP kinase activation in a dose-dependent manner in the range between 0.1 nmol/L and 0.1 micromol/L. PD98059, a specific inhibitor of the upstream kinase that activates p42/p44 MAP kinase, suppressed endothelin-1-induced IL-6 synthesis as well as endothelin-1-activated p42/p44 MAP kinase. Both p42/p44 MAP kinase activation and IL-6 synthesis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C-activating phorbol ester, were reduced by PD98059. Calphostin C, a highly specific inhibitor of protein kinase C, suppressed endothelin-1-stimulated p42/p44 MAP kinase activation as well as endothelin-1-induced IL-6 synthesis. These results strongly suggest that protein kinase C-dependent p42/p44 MAP kinase activation is involved in endothelin-1-induced IL-6 synthesis in osteoblast-like cells.
Kawamura
H
H
Department of Pharmacology, Gifu University School of Medicine, Japan.
Otsuka
T
T
Tokuda
H
H
Matsuno
H
H
Niwa
M
M
Matsui
N
N
Uematsu
T
T
Kozawa
O
O
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D019332:Endothelin-1 / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009281:Naphthalenes / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015850:Interleukin-6; D009281:Naphthalenes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one