IL-17A promotes microglial activation and neuroinflammation in mouse models of intracerebral haemorrhage
IL-17A promotes microglial activation and neuroinflammation in mouse models of intracerebral haemorrhage
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IL-17A促进脑出血小鼠模型中的小胶质细胞活化和神经炎症
DOI：
10.1016/j.molimm.2016.04.003
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yang Zhao
中科院分区：
文献类型：
--
作者：
Yu Anyong;Duan Haizhen;Zhang Tianxi;Pan Yong;Kou Zhi;Zhang Xiaojun;Lu Yuanlan;Wang Song;Yang Zhao
小胶质细胞激活是脑出血（ICH）神经炎症的重要因素。IL-17A已被证实与多发性硬化症等神经炎性疾病有关。然而，IL-17A在脑出血中介导的小胶质细胞活化的确切机制尚未得到很好的确定。本实验旨在探讨IL-17A在脑出血诱导的小胶质细胞活化和神经炎症中的作用。采用自体血液注射法制备脑出血小鼠模型。观察脑出血后小鼠血肿周围区IL-17A表达、炎症因子及神经功能变化。此外，il - 17a中和抗体被用来潜在地阻止脑出血小鼠的小胶质细胞激活和神经炎症。脑出血后，IL-17A的表达、炎症因子的表达和血肿周围小胶质细胞的活化明显增加，神经功能受损。此外，IL-17A Ab可抑制ich诱导的细胞因子TNF-α、IL-1β和IL-6的表达，以及下游信号分子MyD88、TRIF、i -κ b α和NF-κBp65的表达，并减弱小胶质细胞的活化。IL-17A Ab显著降低脑出血小鼠脑含水量，改善神经功能。总之，我们的结果表明IL-17A参与了ich诱导的小胶质细胞激活和神经炎症。IL-17A Ab也可能为脑出血提供一种有希望的治疗策略。
Microglial activation is an important contributor to neuroinflammation in intracerebral haemorrhage (ICH). IL-17A has been demonstrated to be involved in neuroinflammatory diseases such as multiple sclerosis. However, the exact mechanism of IL-17A mediated microglial activation in ICH has not been well identified. The purpose of this experiment is to investigate the role of IL-17A in ICH induced microglial activation and neuroinflammation. ICH mice were made by injection of autologous blood model. IL-17A expression and inflammatory factors in perihematomal region, and neurological function of mice were examined after ICH. In addition, IL-17A-neutralizing antibody was utilized to potentially prevent microglial activation and neuroinflammation in ICH mice. The expression of IL-17A, inflammatory factors and microglial activation in perihematomal region were significantly increased, and neurological function of mice was impaired after ICH. In addition, IL-17A Ab prevented ICH-induced cytokine expression, including TNF-α, IL-1β and IL-6, and downstream signaling molecules, including MyD88, TRIF, IκBα, and NF-κBp65 expression, and attenuated microglial activation. IL-17A Ab significantly reduced brain water content and improved neurological function of ICH mice. In conclusion, our results demonstrated that IL-17A was involved in ICH-induced microglial activation and neuroinflammation. IL-17A Ab might also provide a promising therapeutic strategy in ICH.