The effects of insulin on the inflammatory activity of BV2 microglia.

The effects of insulin on the inflammatory activity of BV2 microglia.
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DOI:
10.1371/journal.pone.0201878
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Byrnes KR
Byrnes KR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brabazon F;Bermudez S;Shaughness M;Khayrullina G;Byrnes KR

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小胶质细胞是中枢神经系统(CNS)的巨噬细胞,其功能是监测和维持动态平衡。小胶质细胞在中枢神经系统损伤、感染或疾病后被激活。长期的小胶质细胞激活对中枢神经系统是有害的,因为它们产生一氧化氮(NO)、活性氧(ROS)和促炎细胞因子,导致神经细胞功能障碍和死亡。小胶质细胞的激活与创伤性脑损伤(TBI)和阿尔茨海默病后的神经功能障碍有关。鼻腔注射胰岛素是治疗阿尔茨海默病和脑外伤的一种很有前途的方法。然而,胰岛素对小胶质细胞的确切作用目前尚不清楚。因此,这项研究的目的是检查胰岛素对激活的小胶质细胞的影响。小胶质细胞系BV2暴露于促炎刺激--脂多糖(LPS),然后注射胰岛素。结果测量在治疗后24小时进行。体外测定NO和ROS的生成。免疫印迹、免疫细胞化学和吞噬实验进一步检测了胰岛素对小胶质细胞活性的影响。胰岛素治疗可显著降低NO、ROS和肿瘤坏死因子α的生成,增强吞噬功能。胰岛素治疗也显著降低iNOS的表达,但对所检测的任何其他M1或M2巨噬细胞极化标志物没有显著影响。这些数据表明,胰岛素具有非常特异的作用,可以减少小胶质细胞的促炎或趋化特性,这可能是胰岛素在中枢神经系统损伤或神经退行性疾病中发挥有益作用的机制之一。
Microglia are the macrophages of the central nervous system (CNS), which function to monitor and maintain homeostasis. Microglial activation occurs after CNS injury, infection or disease. Prolonged microglial activation is detrimental to the CNS as they produce nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines, resulting in neuronal cell dysfunction and death. Microglial activation is implicated in the neurological deficits following traumatic brain injury (TBI) and Alzheimer’s disease. Intranasal insulin administration is a promising treatment of Alzheimer’s disease and TBI. However, the exact effect of insulin on microglia is currently unclear. The goal of this study was therefore to examine the effect of insulin administration on activated microglia. The microglial cell line BV2 were exposed to a pro-inflammatory stimulus, lipopolysaccharide (LPS), followed by insulin administration. Outcome measures were conducted at 24 hours after treatment. In vitro assays quantified NO and ROS production. Western blot, immunocytochemistry and phagocytosis assay further examined the effect of insulin on microglial activity. Insulin treatment significantly reduced NO, ROS and TNFα production and increased phagocytic activity. Insulin treatment also significantly reduced iNOS expression, but had no significant effect on any other M1 or M2 macrophage polarization marker examined. These data suggest that insulin has very specific effects to reduce pro-inflammatory or chemoattractant properties of microglia, and this may be one mechanism by which insulin has beneficial effects in CNS injury or neurodegenerative conditions.
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