Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death.
Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death.
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DOI：
10.1038/srep43153
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Iribarren P
中科院分区：
文献类型：
--
作者：
Bussi C;Peralta Ramos JM;Arroyo DS;Gaviglio EA;Gallea JI;Wang JM;Celej MS;Iribarren P
自噬是一种基本的细胞内稳态机制，细胞通过自消化部分细胞质来去除或周转。神经退行性疾病与自噬失调相关，并且调节自噬的药物已经在几种动物模型中获得成功。小胶质细胞是中枢神经系统（CNS）中的吞噬细胞，在病理条件下被激活并决定其他神经细胞的命运。在这里，我们研究了自噬对小胶质细胞中促炎分子产生的影响及其对神经元细胞的影响。我们观察到，海藻糖和雷帕霉素都激活BV 2小胶质细胞中的自噬，并下调促炎细胞因子和一氧化氮（NO）的产生，以响应LPS和α-突触核蛋白。自噬还调节了BV 2细胞中p38和ERK 1/2 MAPK的磷酸化，这是NO产生所必需的。自噬的这些作用改变了小胶质细胞活化对神经元细胞的影响，从而抑制了神经毒性。我们的研究结果表明，自噬在调节小胶质细胞活化和促炎分子分泌中的新作用，这可能对控制CNS中的炎症反应和神经毒性很重要。
Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells. We observed that both trehalose and rapamycin activate autophagy in BV2 microglial cells and down-regulate the production of pro-inflammatory cytokines and nitric oxide (NO), in response to LPS and alpha-synuclein. Autophagy also modulated the phosphorylation of p38 and ERK1/2 MAPKs in BV2 cells, which was required for NO production. These actions of autophagy modified the impact of microglial activation on neuronal cells, leading to suppression of neurotoxicity. Our results demonstrate a novel role for autophagy in the regulation of microglial cell activation and pro-inflammatory molecule secretion, which may be important for the control of inflammatory responses in the CNS and neurotoxicity.