Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways
Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways
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DOI：
10.3109/08923973.2016.1168433
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发表时间：
2016-04
影响因子：
3.3
通讯作者：
Wei Zhu;Jie Li;Yigang Liu;Kun Xie;Le Wang;Jianmin Fang
中科院分区：
文献类型：
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作者：
Wei Zhu;Jie Li;Yigang Liu;Kun Xie;Le Wang;Jianmin Fang
摘要中脑星形胶质细胞源性神经营养因子（MANF）是一种新的进化保守的神经营养因子（NTF），在帕金森病（PD）等神经退行性疾病模型中具有保护中脑多巴胺能神经元的作用。神经干细胞（neural stem cells，NSCs）是治疗神经退行性疾病的重要工具，但中枢神经系统（central nervous system，CNS）的炎症反应损害了NSCs的功能。虽然已有研究表明MANF对中枢神经系统神经元具有保护作用，但对MANF对神经干细胞的作用尚缺乏深入研究。本研究旨在探讨MANF对脂多糖（LPS）诱导的神经干细胞的增殖反应及其信号转导机制。结果表明，MANF通过调节NF-κB和p38丝裂原活化蛋白激酶（MAPK）的磷酸化途径，而非p-JNK和p-ERK信号通路，降低LPS诱导的IL-1β、TNF-α和IFN-γ等促炎细胞因子的表达。这些结果表明，MANF可以促进保护神经干细胞的炎症反应，为神经干细胞在治疗中的应用提供了有益的功能。
Abstract Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new evolutionary conserved neurotrophic factor (NTF), has been reported to protect midbrain dopaminergic neurons of neurodegenerative diseases such as Parkinson’s disease (PD) model. Neural stem cells (NSCs) can play a role as the therapeutic tool in neurodegenerative diseases, but the inflammatory responses of central nervous system (CNS) appear to harm this function. Although studies have previously demonstrated the protective effect of MANF on neurons of CNS, it is lacking in making great efforts on the function of MANF on NSCs. The aim of this study was to investigate the antiinflammatory responses and signaling mechanisms of MANF on lipopolysaccharide (LPS)-induced NSCs. In the results, MANF decreased the proinflammatory cytokines of IL-1β, TNF-α, and IFN-γ induced by LPS by regulating NF-κB and phosphorylation of p38-mitogen-activated protein kinases (MAPKs) pathways, neither p-JNK nor p-ERK signaling. These findings suggest that MANF can facilitate to protect the inflammatory responses of NSCs, and provide beneficial function for the application of NSCs in the therapy.