Interleukin 17A exacerbates ER‐stress‐mediated inflammation of macrophages following ICH
Interleukin 17A exacerbates ER‐stress‐mediated inflammation of macrophages following ICH
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DOI：
10.1016/j.molimm.2018.05.020
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发表时间：
2018-09
影响因子：
3.6
通讯作者：
zhao yang;Qingjun Liu;Hui Shi;Xuheng Jiang;Song Wang;Yuanlan Lu;Ji Zhang;Xiaofei Huang;Anyong Yu
中科院分区：
文献类型：
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作者：
zhao yang;Qingjun Liu;Hui Shi;Xuheng Jiang;Song Wang;Yuanlan Lu;Ji Zhang;Xiaofei Huang;Anyong Yu
IL-17 A有助于脑出血（ICH）后炎症的启动。内质网（ER）应激作用于蛋白质折叠并导致炎症性疾病。IL-17 A在ICH后ER应激调节中的作用尚未得到很好的表征。本研究用IL-17 A刺激巨噬细胞，然后在体外测定ER应激和下游促炎因子。此外，在体内评估脑出血小鼠的脑水肿和脑损伤。我们证明IL-17 A在体外诱导巨噬细胞的ER应激，从而促进炎症。相反，IL-17 A抑制减弱ER应激和神经炎症。此外，ERK 1/2和p38 MAPK途径介导IL-17 A诱导的巨噬细胞ER应激。IL-17 A抑制剂可明显减轻脑出血小鼠的内质网应激和脑损伤，提示IL-17 A可增加巨噬细胞的内质网应激，是脑出血的一种新机制。
IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measuredin vitro. In addition, brain edema and brain injury in ICH mice were assessedin vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammationin vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice.In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH.