M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain.
M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain.
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DOI：
10.5607/en.2017.26.1.33
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发表时间：
2017-02
影响因子：
2.4
通讯作者：
Lee JE
中科院分区：
文献类型：
--
作者：
Choi JY;Kim JY;Kim JY;Park J;Lee WT;Lee JE
小胶质细胞在缺血性脑卒中的免疫反应和炎症反应中起关键作用。活化的小胶质细胞促进受损脑组织中的神经元损伤或保护。细胞外信号使小胶质细胞趋向M1/M2表型。M1/M2表型小胶质细胞释放促炎和抗炎细胞因子，诱导神经干/祖细胞（NSPCs）的活化。在这项研究中，我们研究了小胶质细胞释放的细胞因子如何影响NSPCs的活化。首先，我们用脂多糖（LPS; 20 ng/ml）处理BV 2细胞中的M1表型小胶质细胞，用白细胞介素-4（IL-4; 20 ng/ml）处理BV 2细胞中的M2表型小胶质细胞。使小鼠经受短暂大脑中动脉闭塞（tMCAO）1小时。在离体条件下，将含有脑室下区（SVZ）的脑切片在M1和M2表型条件培养基中培养3 d。采用RT-PCR和ELISA方法检测细胞因子在条件培养液中的表达。M2表型小胶质细胞条件培养基导致缺血性卒中后同侧SVZ中NSPCs的增殖和神经分化。RT-PCR和ELISA结果显示，M2型小胶质细胞条件培养液中TGF-α mRNA的表达量显著增加。这些结果支持M2型小胶质细胞源性TGF-α是促进缺血性脑卒中后NSPCs增殖和神经分化的关键因素之一。
Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke. Activated microglia promote neuronal damage or protection in injured brain tissue. Extracellular signals polarize the microglia towards the M1/M2 phenotype. The M1/M2 phenotype microglia released pro- and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs). In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs. First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotype-conditioned media for 3 d. We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA. The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke. The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media. These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.