钙离子ATP酶抑制剂对骨髓源性肥大细胞释放单核细胞趋化蛋白-1的影响及p38丝裂原活化蛋白激酶激活的参与情况

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

作者信息

Teshima R, Onose J, Okunuki H, Sawada J

机构信息

Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.

出版信息

Int Arch Allergy Immunol. 2000 Jan;121(1):34-43. doi: 10.1159/000024295.

DOI:10.1159/000024295

PMID:10686507

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+)) 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.

摘要

研究了两种Ca(2+)ATP酶抑制剂，环匹阿尼酸（CPA）和2,5-二-（叔丁基）-1,4-对苯二酚（DTBHQ）对骨髓来源肥大细胞（BMMCs）释放单核细胞趋化蛋白-1（MCP-1）的影响。CPA和DTBHQ增加细胞内游离Ca(2+)浓度（[Ca(2+)]i），并以剂量依赖方式诱导MCP-1释放。与它们诱导肿瘤坏死因子-α（TNF-α）不同，这些Ca(2+)ATP酶抑制剂在没有佛波酯的情况下诱导MCP-1释放。MCP-1释放在6-9小时达到最大值。用放线菌素D、免疫抑制剂环孢菌素A和胞质Ca(2+)螯合剂BAPTA-AM处理可抑制其释放。此外，逆转录聚合酶链反应（RT-PCR）显示MCP-1信使核糖核酸（mRNA）呈时间依赖性增加。因此，MCP-1释放似乎依赖于Ca(2+)依赖性转录激活。MCP-1释放受到p38丝裂原活化蛋白激酶（MAP）抑制剂SB202190的剂量依赖性抑制，但不受p44/42 MAP激酶抑制剂PD98059的抑制。因此，MCP-1产生的转录激活及其释放似乎依赖于活化T细胞核因子和p38 MAP激酶激活。这是首次报道显示BMMCs中MCP-1产生的调控。