Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage.
Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage.
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Peli1 在实验性蛛网膜下腔出血后小胶质细胞激活、神经炎症反应和神经功能缺损中的作用
DOI：
10.3389/fnmol.2017.00398
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发表时间：
2017
影响因子：
4.8
通讯作者：
Sun XC
中科院分区：
文献类型：
--
作者：
Huang XP;Peng JH;Pang JW;Tian XC;Li XS;Wu Y;Li Y;Jiang Y;Sun XC
蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）与神经炎症密切相关。小胶质细胞活化是SAH后导致神经炎症的早期事件。Peli 1是一种E3泛素连接酶，介导小胶质细胞中促炎细胞因子的诱导。在这里，我们报告了Peli 1在SAH介导的大脑病理学中的贡献。在成年雄性C57 BL/6 J小鼠中通过血管内穿孔诱导SAH模型。Peli 1在小鼠脑中以时间依赖性方式被显著诱导，并且主要在SAH后的CD 16/32阳性小胶质细胞中表达。使用遗传学方法，我们证明了Peli 1的减少显著改善了神经功能缺损，减轻了脑水肿，减少了促炎细胞因子IL-6的过度表达，并改变了凋亡/抗凋亡生物标志物。此外，Peli 1下调通过下调cIAP 1/2表达抑制ERK和JNK磷酸化水平，随后降低SAH后诱导型一氧化氮合酶（iNOS）的表达。因此，这些研究结果表明Peli 1通过介导cIAP 1/2激活，从而促进实验性SAH后MyD 88依赖性MAPK通路的激活，在EBI中参与小胶质细胞介导的神经炎症。Peli 1可促进SAH后M1小胶质细胞极化生物标志物CD 16/32和iNOS的表达。靶向Peli 1在SAH后EBI期间发挥神经保护作用，因此可能为高危个体的预防-治疗提供潜在的选择。
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is closely associated with neuroinflammation. Microglial activation is an early event that leads to neuroinflammation after SAH. Peli1 is an E3 ubiquitin ligase that mediates the induction of pro-inflammatory cytokines in microglia. Here we report Peli1 contributions in SAH mediated brain pathology. An SAH model was induced by endovascular perforation in adult male C57BL/6J mice. Peli1 was markedly induced in mice brains in a time-dependent manner and was predominantly expressed in CD16/32-positive microglia after SAH. Using genetic approaches, we demonstrated that decreased Peli1 significantly improved neurological deficits, attenuated brain edema, reduced over-expression of pro-inflammatory cytokine IL-6 and modified apoptotic/antiapoptotic biomarkers. In addition, Peli1 downregulation suppressed ERK and JNK phosphorylation levels via the downregulation of cIAP1/2 expression, subsequently reducing inducible nitric oxide synthase (iNOS) expression after SAH. Therefore, these findings demonstrate that Peli1 contributes to microglia-mediated neuroinflammation in EBI by mediating cIAP1/2 activation, thus promoting the activation of MyD88-dependent MAPK pathway after experimental SAH. Our findings also showed that Peli1 could promote the expression of M1 microglia polarization biomarker CD16/32 and iNOS after SAH. Targeting Peli1 exerts neuroprotective effects during EBI after SAH, thus could provide potential option for prevention-therapy in high-risk individuals.
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影响因子：
4.8
作者：
Murphy, Michael;Xiong, Yanbao;Medvedev, Andrei E.
通讯作者：
Medvedev, Andrei E.
影响因子：
44.1
作者：
Hu H;Sun SC
通讯作者：
Sun SC
PELI1促进了TRIF依赖性Toll样受体信号传导和促炎性细胞因子的产生。
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
1.5
作者：
Sabri M;Lass E;Macdonald RL
通讯作者：
Macdonald RL
影响因子：
8.7
作者：
Medvedev AE;Murphy M;Zhou H;Li X
通讯作者：
Li X