Notch1信号通过TRAF6参与TLR4介导的NF-κB激活

发布时间：2018-01-12 01:34

本文关键词：Notch1信号通过TRAF6参与TLR4介导的NF-κB激活　出处：《免疫学杂志》2017年08期 　论文类型：期刊论文

更多相关文章：炎症 Notch TLR TRAF NF-κB

【摘要】：目的观察Notch1和TLR4信号交叉调控NF-κB激活并探讨其可能的作用机制。方法体外培养RAW264.7细胞,LPS刺激RAW264.7细胞后检测Notch1信号激活以及Notch1信号抑制剂DAPT对TNF-α、IL-6和IL-1β表达的影响,Western blot检测DAPT对IKKα/β磷酸化以及NF-κB p65活化的影响,并检测DAPT对TLR4信号通路IKKα/β上游信号My D88和TRAF6表达的影响。结果 LPS刺激RAW264.7细胞后能显著提高Notch1信号蛋白NICD和目的蛋白Hes1表达,DAPT能明显抑制NICD和Hes1的表达。LPS诱导TNF-α、IL-6和IL-1β表达和释放能被DAPT抑制但被Notch1信号激动剂jagged1增强。DAPT能够抑制LPS介导的TRAF6表达和IKKα/β磷酸化,促进NF-κB p65核转位,但DAPT对LPS诱导My D88的表达没有明显的影响。结论 Notch1和TLR4信号存在交叉对话,Notch1通过TRAF6调控NF-κB活化参与TLR4介导的免疫应答。
[Abstract]:Objective to observe the cross-regulation of NF- 魏 B by Notch1 and TLR4 signals and to explore its possible mechanism. Methods RAW264.7 cells were cultured in vitro. After LPS stimulated RAW264.7 cells, the activation of Notch1 signal and the effect of Notch1 signal inhibitor DAPT on the expression of IL-6 and IL-1 尾 were detected. The effects of DAPT on IKK 伪 / 尾 phosphorylation and NF- 魏 B p65 activation were detected by Western blot. The effect of DAPT on the expression of IKK 伪 / 尾 upstream signal my D88 and TRAF6 in TLR4 signaling pathway was detected. LPS stimulated RAW264.7 cells significantly increased the expression of Notch1 signal protein NICD and target protein Hes1. DAPT could significantly inhibit the expression of NICD and Hes1. LPS-induced TNF- 伪. IL-6 and IL-1 尾 expression and release can be inhibited by DAPT but enhanced by Notch1 signal agonist jagged1. DAPT can inhibit LPS mediated TRAF6 expression and IK. K 伪 / 尾 phosphorylation. The nuclear translocation of NF- 魏 B p65 was promoted, but DAPT had no significant effect on the expression of my D88 induced by LPS. Conclusion there is a cross-talk between Notch1 and TLR4 signals. Notch1 regulates NF- 魏 B activation through TRAF6 and participates in TLR4 mediated immune response.
【作者单位】：延边大学附属医院神经内科;延边大学中医学院临床教研室;延边大学医学院解剖学教研室;
【基金】：国家自然科学基金(81560004) 吉林省科技厅项目(20160101210JC) 吉林省卫生计生委青年项目(2015Q028)
【分类号】：R392
【正文快照】： 炎症是机体免疫系统防御外来刺激和组织损伤而表现出的一个复杂过程。Toll样受体(TLR)作为模式识别受体表达在单核/巨噬细胞、抗原呈递细胞、淋巴细胞等细胞表面,能够识别病原相关分子模式,引发信号转导,诱导炎症介质的产生,在天然免疫或获得性免疫中发挥重要作用。Notch信号

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