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

作者全名："Xia, Xiaohui; Yang, Zhao; Zhang, Jiangwei; Fu, Xiongjie; Han, Bin; Xiong, Qijiang; Yu, Anyong"

作者地址："[Xia, Xiaohui; Yang, Zhao; Zhang, Jiangwei; Fu, Xiongjie; Han, Bin; Xiong, Qijiang] Chongqing Med Univ, Yongchuan Hosp, Dept Neurosurg, Chongqing 402160, Peoples R China; [Yu, Anyong] Zunyi Med Univ, Afffliated Hosp, Dept Emergency, Zunyi 563003, Guizhou, Peoples R China"

通信作者："Xiong, QJ (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Dept Neurosurg, Chongqing 402160, Peoples R China.; Yu, AY (通讯作者)，Zunyi Med Univ, Afffliated Hosp, Dept Emergency, Zunyi 563003, Guizhou, Peoples R China."

来源：IMMUNOLOGY LETTERS

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001113497200001

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：264

期号：　

开始页：36

结束页：45

文献类型：Article

关键词：Nedd4L; TRAF3; M1 polarization; Intracerebral hemorrhage; Neuroinflammation; Blood-brain barrier

摘要："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-kappa B 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."

基金机构："National Natural Science Foundation of China [82260254, Ycstc2020nb0255, 2023yc-jckx20051, CSTB2023NSCQ-MSX0711]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (82260254) and Ycstc2020nb0255 and 2023yc-jckx20051 and CSTB2023NSCQ-MSX0711.