Interaction of Wip1 and NF-κB regulates neuroinflammatory response in astrocytes
Interaction of Wip1 and NF-κB regulates neuroinflammatory response in astrocytes
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Wip1 和 NF-kappa B 的相互作用调节星形胶质细胞的神经炎症反应
DOI：
10.1007/s00011-017-1085-8
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发表时间：
2017-11-01
影响因子：
6.7
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Xu, Fan;Chen, Lifei;Li, Min
本研究旨在探讨Wip1与核因子-kappa B p65在脂多糖(LPS)诱导的大鼠视网膜星形胶质细胞活化模型中的相互作用。用Western印迹和RT-PCR检测Wip1和NF-kappa B p65的表达。将针对Wip1的小干扰RNA(SiRNA)导入星形胶质细胞，以明确核转录因子-kappaBp65的磷酸化状态、核转位以及这些促炎因子的表达。同时，用核因子-kappaB抑制剂处理后检测Wip1的表达，内毒素处理后，Wip1和磷酸化的核因子-kappaBp65(p-p65)的表达显著增加，并共存于星形胶质细胞。转染Wip1 siRNA后加入脂多糖，可增强p-p65的表达。此外，Wip1 siRNA的预处理进一步增强了内毒素诱导的NF-kappa B p65移位到细胞核内和促炎细胞因子的释放。最后，抑制核因子-kappa B降低了Wip1在原代星形胶质细胞中的表达和转录。这些数据为Wip1和核因子-kappaB负反馈环在脂多糖诱导的星形胶质细胞激活中的作用机制提供了机制。
The aims of the present study were to detect the interaction of Wip1 and NF-kappa B P65 in retina of an LPS-induced astrocytes activation model.The interaction between Wip1 and nuclear factor kappa B (NF-kappa B) P65 was observed in lipopolysaccharide (LPS)-stimulated primary rat astrocytes derived from retina. The expressions of Wip1 and NF-kappa B P65 were evaluated using Western blot and RT-PCR. Small interfering RNA (siRNA) against Wip1 was transfected into astrocytes to clarify the phosphorylation status and nuclear translocation of NF-kappa B P65 and expressions of these proinflammatory factors. Meanwhile, expression of Wip1 was assessed following treatment with NF-kappa B inhibitor.Wip1 and phospho-NF-kappa B P65 (p-P65) expressions were significantly increased and colocalization in astrocytes after LPS treatment. The expression of p-P65 was augmented by transfected with Wip1 siRNA followed by LPS. Furthermore, pre-treatment with Wip1 siRNA further enhanced LPS-induced NF-kappa B P65 translocation into the nuclei and proinflammatory cytokine release. Finally, inhibition of NF-kappa B decreases Wip1 expression and transcription in primary astrocytes.These data provide a mechanism for the role for a negative feedback loop of Wip1 and NF-kappa B in LPS-induced astrocytic activation.