title: Activation of mitogen-activated protein kinase is involved in sphingosine 1-phosphate-stimulated interleukin-6 synthesis in osteoblasts.
abstract: We previously showed that sphingosine 1-phosphate (SPP) acts as a second messenger for tumor necrosis factor alpha-induced interleukin-6 (IL-6) synthesis in osteoblast-like MC3T3-E1 cells. In the present study, we further investigated the mechanism of IL-6 synthesis induced by SPP in MC3T3-E1 cells. SPP significantly induced p42/p44 mitogen-activated protein (MAP) kinase activity. PD98059, an inhibitor of MAP kinase kinase, suppressed SPP-induced IL-6 synthesis as well as SPP-induced MAP kinase activation. The patterns of both inhibitions were similar. TMB-8, an inhibitor of Ca2+ mobilization from intracellular Ca2+ stores, significantly suppressed the SPP-induced IL-6 synthesis. These results strongly suggest that SPP-induced IL-6 synthesis is mediated via p42/p44 MAP kinase activation in osteoblast-like cells and that the SPP-induced IL-6 synthesis is dependent on intracellular Ca2+ mobilization.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Aichi, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
authors.forename: H
authors.initials: H
authors.lastname: Tokuda
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008246:Lysophospholipids; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015850:Interleukin-6; D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; C060506:sphingosine 1-phosphate; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D013110:Sphingosine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium