Abstract

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.

中文翻译：

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外源HSP70和信号通路参与抑制脂多糖诱导的神经母细胞瘤细胞神经毒性。

摘要

神经炎症在神经退行性疾病的发病机理中起关键作用。小胶质细胞是中枢神经系统的主要免疫细胞。暴露于脂多糖（LPS，革兰氏阴性肠杆菌细胞壁的成分）后，小胶质细胞被激活产生活性氧（ROS），细胞因子和炎性介质，这可能会导致神经元死亡。测试了外源重组人类热休克蛋白70（HSP70）对人小胶质细胞和神经母细胞瘤细胞响应大肠杆菌LPS活化的影响。实验包括分别进行细胞培养，并将条件培养基从A-172小胶质细胞转移到SK-N-SH神经母细胞瘤细胞，以模拟用LPS和/或HSP70处理的小胶质细胞的作用。在有或没有HSP70的情况下，估计LPS处理的细胞中ROS，TNFα和细胞凋亡的水平。HSP70被发现可以减少LPS诱导的ROS生成，TNFα的产生，凋亡和坏死，无论是在单独的细胞培养还是在小胶质细胞的条件培养基中生长的成神经细胞瘤细胞中。已证明涉及蛋白激酶p38MAPK，JNK和PI3K的信号通路在HSP70介导的保护小胶质细胞和神经母细胞瘤细胞免受LPS诱导的凋亡和ROS产生中起重要作用。