title: Effect of Ca(2+) ATPase inhibitors on MCP-1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation.
abstract: The effect of two Ca(2+) ATPase inhibitors, cyclopiazonic acid (CPA) and 2,5-di-(tert-butyl)-1,4-hydroquinone (DTBHQ), on the release of MCP-1 from bone marrow-derived mast cells (BMMCs) were investigated. CPA and DTBHQ increased the intracellular free Ca(2+) concentration ([Ca(2+)](i)) and induced MCP-1 release in a dose-dependent manner. These Ca(2+) ATPase inhibitors induced MCP-1 release in the absence of phorbol ester, in contrast to their induction of TNF-alpha. MCP-1 release reached a maximum at 6-9 h. It was inhibited by treatment with actinomycin D, the immunosuppressant cyclosporin A, and the cytosolic Ca(2+) chelator BAPTA-AM. Furthermore, RT-PCR showed a time-dependent increase of MCP-1 mRNA. Thus MCP-1 release seems to depend on Ca(2+)-dependent transcriptional activation. MCP-1 release was dose-dependently inhibited by the p38 MAP kinase inhibitor SB202190, but not by the p44/42 MAP kinase inhibitor PD98059. Therefore, transcriptional activation of MCP-1 production and its release seem to be dependent on the nuclear factor of activated T cells and p38 MAP kinase activation. This is the first report to show the regulation of MCP-1 production in BMMCs.
authors.affiliation: Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. rteshima@nihs.go.jp
authors.forename: R
authors.initials: R
authors.lastname: Teshima
authors.forename: J
authors.initials: J
authors.lastname: Onose
authors.forename: H
authors.initials: H
authors.lastname: Okunuki
authors.forename: J
authors.initials: J
authors.lastname: Sawada
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007211:Indoles; D012333:RNA, Messenger; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D003609:Dactinomycin; C019359:2,5-di-tert-butylhydroquinone; D004533:Egtazic Acid; D016572:Cyclosporine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid