Corticosterone suppresses the proliferation of BV2 microglia cells via glucocorticoid, but not mineralocorticoid receptor.
Corticosterone suppresses the proliferation of BV2 microglia cells via glucocorticoid, but not mineralocorticoid receptor.
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DOI：
10.1016/j.lfs.2012.08.019
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发表时间：
2012-10
期刊：
影响因子：
6.1
通讯作者：
Y. Nakatani;T. Amano;M. Tsuji;H. Takeda
中科院分区：
文献类型：
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作者：
Y. Nakatani;T. Amano;M. Tsuji;H. Takeda
AIMSCorticosterone（CORT），通常被称为应激激素，是一种众所周知的外周免疫反应调节剂，也在大脑中显示出抗炎特性。小胶质细胞在大脑中的免疫反应和炎症中起关键作用。然而，目前还不清楚CORT如何影响小胶质细胞。本研究以小鼠小胶质细胞系BV 2为材料，观察CORT对小胶质细胞增殖和存活的影响。主要方法采用WST-8和乳酸脱氢酶（LDH）法检测CORT对BV 2小胶质细胞增殖和存活的影响。用0.1、1和10μM CORT处理BV 2细胞24 h后，BV 2细胞增殖率分别为对照组的83%、77%和70%。此外，这种抑制作用可以通过糖皮质激素受体（GR）拮抗剂米非司酮的治疗来阻断，但不能通过盐皮质激素受体（MR）拮抗剂螺内酯的治疗来阻断。此外，LDH测定显示CORT对BV 2小胶质细胞具有剂量依赖性的细胞毒性，米非司酮治疗可部分消除这种细胞毒性。此外，CORT治疗导致GR易位，但不是MR，从胞浆到nucleus. SIGNIFICANCE我们的研究结果表明，CORT抑制BV 2小胶质细胞的增殖伴随着细胞毒性作用，这是诱导的CORT-GR复合物的形成。
AIMSCorticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. Microglia play a key role in immune response and inflammation in the brain. However, it is still unclear how CORT affects microglia. In this study, we focused on the effects of CORT on the proliferation and survival of microglia using mouse microglia cell line BV2.MAIN METHODSWe used WST-8 and LDH (lactate dehydrogenase) assays to check the effects of CORT for the proliferation and survival in BV2 microglia cells. We also analyzed the expression pattern of proteins which related to CORT signal cascades using western blotting analysis.KEY FINDINGSUnder treatment with 0.1, 1 and 10μM CORT for 24h, the BV2 proliferation rate decreased to 83, 77 and 70% of that in the control. Moreover, this inhibition was blocked by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist. Moreover, an LDH assay showed that CORT was dose-dependently cytotoxic toward BV2 microglia cells and this cytotoxicity was partially abolished by treatment with mifepristone. In addition, treatment with CORT resulted in the translocation of GR, but not MR, from the cytosol to the nucleus.SIGNIFICANCEOur findings suggested that CORT suppresses the proliferation of BV2 microglia cells accompanied with a cytotoxic effect that is induced by the formation of a CORT–GR complex.