Statin treatment affects cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms.
Statin treatment affects cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms.
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DOI：
10.1186/s13041-014-0085-7
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发表时间：
2014-11-26
期刊：
影响因子：
3.6
通讯作者：
Todd KG
中科院分区：
文献类型：
--
作者：
Churchward MA;Todd KG
作为中枢神经系统的主要免疫细胞，小胶质细胞有助于中枢神经系统的发育、稳态和可塑性，除了它们在异物和炎症反应中的充分表征的作用之外。越来越多地报道，小胶质细胞的不适当激活是神经退行性疾病和神经精神疾病中炎症的一个组成部分。他汀类降胆固醇药物已被观察到在神经退行性疾病和缺血性中风中具有抗炎和保护作用，并被认为通过减弱小胶质细胞活性起作用。我们试图研究辛伐他汀治疗对原代培养的大鼠小胶质细胞的分泌特征和吞噬活性的影响，并剖析辛伐他汀对小胶质细胞活性的作用机制。辛伐他汀治疗以胆固醇依赖性方式改变了小胶质细胞释放的细胞因子和营养因子，包括白细胞介素-1-β、肿瘤坏死因子-α和脑源性神经营养因子。相反，辛伐他汀以非胆固醇依赖的方式抑制小胶质细胞的吞噬作用。细胞因子释放和吞噬作用的胆固醇依赖性的差异表明这两种作用通过不同的分子机制发生。这两种途径可能为进一步完善神经炎性、神经退行性和神经精神疾病的药物治疗提供了机会。
As the primary immune cells of the central nervous system, microglia contribute to development, homeostasis, and plasticity of the central nervous system, in addition to their well characterized roles in the foreign body and inflammatory responses. Increasingly, inappropriate activation of microglia is being reported as a component of inflammation in neurodegenerative and neuropsychiatric disorders. The statin class of cholesterol-lowering drugs have been observed to have anti-inflammatory and protective effects in both neurodegenerative diseases and ischemic stroke, and are suggested to act by attenuating microglial activity. We sought to investigate the effects of simvastatin treatment on the secretory profile and phagocytic activity of primary cultured rat microglia, and to dissect the mechanism of action of simvastatin on microglial activity. Simvastatin treatment altered the release of cytokines and trophic factors from microglia, including interleukin-1-β, tumour necrosis factor-α, and brain derived neurotrophic factor in a cholesterol-dependent manner. Conversely, simvastatin inhibited phagocytosis in microglia in a cholesterol-independent manner. The disparity in cholesterol dependence of cytokine release and phagocytosis suggests the two effects occur through distinct molecular mechanisms. These two pathways may provide an opportunity for further refinement of pharmacotherapies for neuroinflammatory, neurodegenerative, and neuropsychiatric disorders.
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影响因子：
3.3
作者：
Lai, A. Y.;Dibal, C. D.;Todd, K. G.
通讯作者：
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影响因子：
168.9
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3
作者：
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作者：
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通讯作者：
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