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Chemokine C-C motif ligand 2 suppressed the growth of human brain astrocytes under Ischemic/hypoxic conditions via regulating ERK1/2 pathway.
Brain Injury ( IF 1.5 ) Pub Date : 2020-08-04 , DOI: 10.1080/02699052.2020.1797167
Min Yu 1 , Ni Zheng 2 , Dudu Jiang 1 , Lijing Wang 1 , Qing Zhan 1 , Jiangmin Zhao 3
Affiliation  

Primary Objective: Chemokine C-C motif ligand 2 (CCL2) plays a critical role in inflammation-related diseases in the central nervous system (CNS). However, the role of CCL2 in ischemic stroke remains unclear. Research Design: To investigate the role of CCL2 in ischemic stroke, we performed oxygen–glucose deprivation (OGD) on human brain astrocytes. Methods and Procedures: To assess cell proliferation, the CCK-8 assay was performed. Cell apoptosis was determined using flow cytometry. qRT-PCR and western blotting were utilized to measure gene expression. Main Outcomes and Results: Our results suggest that CCL2 and its receptor CCR2 are upregulated in OGD cells. Moreover, a CCL2 antibody significantly alleviated the ischemic/hypoxic-induced suppression of growth in human brain astrocytes. Human recombinant protein, CCL2, inhibited the growth of human brain astrocytes under normoxia conditions. These results demonstrate that CCL2 upregulation suppresses the recovery of human brain astrocytes under ischemic/hypoxic conditions. This effect was abolished by the ERK inhibitor PD98059. Therefore, CCL2/CCR2 activation may suppress the growth of human brain astrocytes through enhancing the activity of ERK1/2. Conclusions: Our results not only developed a deeper understanding of the role of CCL2 in human brain astrocytes but also provided novel insight into potential treatments for ischemic stroke.



中文翻译:

趋化因子CC基序配体2通过调节ERK1/2通路抑制缺血/缺氧条件下人脑星形胶质细胞的生长。

主要目的:趋化因子 CC 基序配体 2 (CCL2) 在中枢神经系统 (CNS) 的炎症相关疾病中起关键作用。然而,CCL2 在缺血性卒中中的作用仍不清楚。研究设计:为了研究 CCL2 在缺血性中风中的作用,我们对人脑星形胶质细胞进行了氧葡萄糖剥夺 (OGD)。方法和程序:为了评估细胞增殖,进行了CCK-8测定。使用流式细胞术测定细胞凋亡。qRT-PCR和蛋白质印迹用于测量基因表达。主要结果和结果:我们的结果表明 CCL2 及其受体 CCR2 在 OGD 细胞中上调。此外,CCL2 抗体显着减轻了缺血/缺氧诱导的人脑星形胶质细胞生长抑制。人重组蛋白,CCL2,在常氧条件下抑制人脑星形胶质细胞的生长。这些结果表明,CCL2 上调抑制了人脑星形胶质细胞在缺血/缺氧条件下的恢复。ERK 抑制剂 PD98059 消除了这种作用。因此,CCL2/CCR2的激活可能通过增强ERK1/2的活性来抑制人脑星形胶质细胞的生长。结论:我们的研究结果不仅加深了对 CCL2 在人脑星形胶质细胞中的作用的理解,而且为缺血性中风的潜在治疗提供了新的见解。CCL2/CCR2的激活可能通过增强ERK1/2的活性来抑制人脑星形胶质细胞的生长。结论:我们的研究结果不仅加深了对 CCL2 在人脑星形胶质细胞中的作用的理解,而且为缺血性中风的潜在治疗提供了新的见解。CCL2/CCR2的激活可能通过增强ERK1/2的活性来抑制人脑星形胶质细胞的生长。结论:我们的研究结果不仅加深了对 CCL2 在人脑星形胶质细胞中的作用的理解,而且为缺血性中风的潜在治疗提供了新的见解。

更新日期:2020-08-22
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