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.

中文翻译：

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E3连接酶Nedd4L通过TRAF3/TBK1信号通路促进小鼠脑出血后巨噬细胞M1极化并加剧脑损伤

背景

脑出血（ICH）是一个严重的医学问题，有希望的治疗策略是有限的。ICH后巨噬细胞引发脑炎症损伤，但其分子机制尚未明确。E3 连接酶 Nedd4L 参与炎症免疫反应的发病机制。

方法

在本研究中，我们检测了 ICH 后巨噬细胞中 Nedd4L 的水平。此外，在 ICH 小鼠中检查了巨噬细胞 M1 极化、促炎细胞因子的产生、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 BBB 破坏以及神经功能缺陷。抑制 Nedd4L 显着减弱体内 M1 极化。抑制 Nedd4L 会降低 TRAF3 和 TBK1 水平，并在 ICH 后降低 p38 和 NF-κB p65 亚基的磷酸化。

结论

我们的数据表明，Nedd4L 参与了 ICH 的发病机制，在 ICH 后，TRAF3 促进了炎症反应并加剧了脑损伤。