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Int Arch Allergy Immunol. 2000 Jan;121(1):34-43.

Effect of Ca(2+) ATPase inhibitors on MCP-1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation.

Author information

1
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. rteshima@nihs.go.jp

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.

PMID:
10686507
DOI:
10.1159/000024295
[Indexed for MEDLINE]

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