Wang Fuli, Awan Umer Farooq, Wang Yuanyuan, Wang Luna, Qing Hong, Ma Hong, Deng Yulin
School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun Nandajie, Haidian District, Beijing 100081, China.
Int J Mol Sci. 2014 Jun 13;15(6):10738-50. doi: 10.3390/ijms150610738.
The adaptive immune system has implications in pathology of Parkinson's disease (PD). Research data demonstrated that the peripheral CD4+ T-cell population decreased in pathogenesis of PD. The effect of damaged dopaminergic neurons on peripheral T cells of PD is still unknown. In this study, we constructed a neuronal and glial cells co-culture model by using human neuroblastoma cells SH-SY5Y and gliomas cells U87. After the co-culture cells were treated with neurotoxin 1-methyl-4-phenylpyridinium (MPP+) for 24 h, the conditioned media was harvested and used to cultivate T-cell leukemia Jurkat cells for another 24 h. We then analyzed the cell proliferation, cell cycle and necrosis effect of Jurkat cells. The results showed that co-culture medium of SH-SY5Y and U87 cells with MPP+ treatment inhibited the proliferation of Jurkat cells compared to control medium without MPP+, even though the same concentration of MPP+ had very little toxicity to the Jurkat cell. Furthermore, co-culture medium with low concentration of MPP+ (100 µM) arrested Jurkat cells cycle in G2/M phase through increasing cell cycle division 2 (CDC2) and CyclinB1 expression level, whereas co-culture medium with high concentration of MPP+ (500 µM) induced Jurkat cell necrosis through cellular swelling and membrane breakage. Our data implies that damaged dopamine neurons with glial cells can lead to the reduced number or inhibited proliferation activity of peripheral T cells.
适应性免疫系统与帕金森病(PD)的病理过程有关。研究数据表明,外周CD4+ T细胞群体在PD发病机制中减少。多巴胺能神经元受损对PD外周T细胞的影响仍不清楚。在本研究中,我们使用人神经母细胞瘤细胞SH-SY5Y和胶质瘤细胞U87构建了神经元和胶质细胞共培养模型。将共培养细胞用神经毒素1-甲基-4-苯基吡啶鎓(MPP+)处理24小时后,收集条件培养基并用于再培养T细胞白血病Jurkat细胞24小时。然后我们分析了Jurkat细胞的细胞增殖、细胞周期和坏死效应。结果表明,与未用MPP+处理的对照培养基相比,经MPP+处理的SH-SY5Y和U87细胞的共培养基抑制了Jurkat细胞的增殖,尽管相同浓度的MPP+对Jurkat细胞的毒性很小。此外,低浓度MPP+(100 µM)的共培养基通过增加细胞周期分裂2(CDC2)和细胞周期蛋白B1表达水平使Jurkat细胞周期停滞在G2/M期,而高浓度MPP+(500 µM)的共培养基通过细胞肿胀和膜破裂诱导Jurkat细胞坏死。我们的数据表明,受损的多巴胺神经元与胶质细胞可导致外周T细胞数量减少或增殖活性受到抑制。