Department of Neurology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine , Shanghai, China.
Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine , Shanghai, China.
Brain Inj. 2020 Jul 28;34(9):1277-1282. doi: 10.1080/02699052.2020.1797167. Epub 2020 Aug 4.
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.
To investigate the role of CCL2 in ischemic stroke, we performed oxygen-glucose deprivation (OGD) on human brain astrocytes.
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.
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.
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.
趋化因子 C-C 基元配体 2（CCL2）在中枢神经系统（CNS）的炎症相关疾病中发挥着关键作用。然而，CCL2 在缺血性中风中的作用尚不清楚。
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）处理。
为了评估细胞增殖，我们进行了 CCK-8 检测。通过流式细胞术检测细胞凋亡。采用 qRT-PCR 和 Western blot 检测基因表达。
我们的结果表明，CCL2 及其受体 CCR2 在 OGD 细胞中上调。此外，CCL2 抗体显著减轻了缺血/缺氧对人脑星形胶质细胞生长的抑制作用。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 的上调抑制了缺血/缺氧条件下人脑星形胶质细胞的恢复。这种作用被 ERK 抑制剂 PD98059 所消除。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。
我们的研究结果不仅加深了对 CCL2 在人脑星形胶质细胞中作用的理解，还为缺血性中风的潜在治疗方法提供了新的思路。
