小鼠脑出血后，E3连接酶Nedd4L通过TRAF3/TBK1信号通路促进巨噬细胞M1极化并加重脑损伤。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2023-11-06 DOI:10.1016/j.imlet.2023.11.002

Xiaohui Xia , Zhao Yang , Jiangwei Zhang , Xiongjie Fu , Bin Han , Qijiang Xiong , Anyong Yu

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引用次数: 0

摘要

背景：脑出血（ICH）是一个严重的医学问题，有希望的策略是有限的。巨噬细胞引发脑出血后的脑炎症损伤，但其分子机制尚未明确。E3连接酶Nedd4L与炎症免疫反应的发病机制有关。方法：在本研究中，我们检测脑出血后巨噬细胞中Nedd4L的水平。此外，在ICH小鼠中检测了巨噬细胞M1极化、促炎细胞因子产生、血脑屏障破坏、脑含水量和神经功能。结果：在这里，我们证明了巨噬细胞的E3连接酶Nedd4L水平在ICH后增加，通过TRAF3促进M1极化炎症。Nedd4L促进血脑屏障破坏以及神经功能缺损。Nedd4L的抑制在体内显著减弱了M1极化。Nedd4L的抑制降低了脑出血后TRAF3和TBK1的水平，以及随后p38和NF-κB p65亚基的磷酸化。

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E3 ligase Nedd4L promotes macrophage M1 polarization and exacerbates brain damage by TRAF3/TBK1 signaling pathway after ICH in mice

Background

Intracerebral hemorrhage (ICH) is a serious medical problem, and promising strategy is limited. Macrophage initiated brain inflammatory injury following ICH, but the molecular mechanism had not been well identified. E3 ligase Nedd4L is implicated in the pathogenesis of the inflammatory immune response.

Methods

In the present study, we detected the levels of Nedd4L in macrophages following ICH. Furthermore, Macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, brain water content and neurological function were examined in ICH mice.

Results

Here, we demonstrated that E3 ligase Nedd4L levels of macrophage increased following ICH, promoted M1 polarization inflammation by TRAF3. Nedd4L promoted BBB disruption, as well as neurological deficits. Inhibition of Nedd4L significantly attenuated M1 polarization in vivo. Inhibition of Nedd4L decreased TRAF3 and TBK1 levels, and subsequent phosphorylation of p38 and NF-κB p65 subunit following ICH.

Conclusions

Our data demonstrated that Nedd4L was involved in the pathogenesis of ICH, which promoted inflammatory responses and exacerbated brain damage by TRAF3 following ICH.

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.