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

Copyright © 2023. Published by Elsevier B.V..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:264

Enthalten in:

Immunology letters - 264(2023) vom: 15. Dez., Seite 36-45

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Blood-brain barrier
EC 2.3.2.26
Intracerebral hemorrhage
Journal Article
M1 polarization
Nedd4 Ubiquitin Protein Ligases
Nedd4L
Nedd4l protein, mouse
Neuroinflammation
TNF Receptor-Associated Factor 3
TRAF3

Anmerkungen:

Date Completed 10.01.2024

Date Revised 10.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.imlet.2023.11.002

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364317477