Inhibition of microglial cell activation by cortisol
Inhibition of microglial cell activation by cortisol
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DOI：
10.1016/s0361-9230(00)00275-6
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发表时间：
2000-07-15
影响因子：
3.8
通讯作者：
Chavis, JA
中科院分区：
文献类型：
--
作者：
Drew, PD;Chavis, JA
皮质醇是一种应对压力而产生的类固醇激素。这种糖皮质激素可能对神经元有毒，因此可能在包括阿尔茨海默病在内的神经退行性疾病中发挥重要作用。激活的小胶质细胞产生一氧化氮（NO）和肿瘤坏死因子- α (tnf - α)等分子，这些分子也可能对神经元有毒。目前的研究旨在确定皮质醇对原代培养的小胶质细胞和转化的N9小胶质细胞激活的影响。研究表明，皮质醇抑制脂多糖（LPS）诱导这些小胶质细胞产生一氧化氮。皮质醇通过抑制诱导型一氧化氮合酶（iNOS）的产生而起作用，iNOS催化NO的合成，皮质醇可能通过阻断iNOS基因表达的转录起作用，因为激素抑制LPS诱导这些细胞中的iNOS RNA水平。激活的小胶质细胞产生增加的tnf - α，除了增加的NO。目前的研究表明，皮质醇可以抑制lps处理的小胶质细胞中tnf - α的释放。总的来说，这些数据表明，尽管皮质醇可能直接对神经元有毒，但这种激素可能通过阻断小胶质细胞产生细胞毒性分子来间接保护神经元。
Cortisol is a steroid hormone produced in response to stress. This glucocorticoid can be toxic to neurons, and thus may be important in neurodegenerative diseases including Alzheimer's disease, Activated microglia produce molecules including nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) which can also be toxic to neurons. The current study was designed to determine the effect of cortisol upon the activation of primary cultured microglia and transformed N9 microglial cells. The studies indicate that cortisol represses lipopolysaccharide (LPS) induction of nitric oxide production in these microglial cells. The hormone acts by inhibiting the production of inducible nitric oxide synthase (iNOS) which catalyses the synthesis of NO, Cortisol likely acts by blocking transcription of iNOS gene expression since the hormone represses LPS induction of iNOS RNA levels in these cells. Activated microglia produce increased TNF-alpha, in addition to increased NO. The current studies demonstrate that cortisol inhibits release of TNF-alpha from LPS-treated microglial cells. collectively, these data suggest that although cortisol may be directly toxic to neurons, the hormone may indirectly protect neurons by blocking the production of cytotoxic molecules by microglia, (C) 2000 Elsevier Science Inc.