泛素连接酶
炎症
发病机制
巨噬细胞极化
免疫系统
磷酸化
巨噬细胞
细胞生物学
癌症研究
医学
化学
免疫学
生物
体外
泛素
生物化学
基因
作者
Xiaohui Xia,Zhao Yang,Jiangwei Zhang,Xiongjie Fu,Baohui Han,Qijiang Xiong,Anyong Yu
标识
DOI:10.1016/j.imlet.2023.11.002
摘要
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. 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. 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. Our data demonstrated that Nedd4L was involved in the pathogenesis of ICH, which promoted inflammatory responses and exacerbated brain damage by TRAF3 following ICH.
科研通智能强力驱动
Strongly Powered by AbleSci AI