A20 ameliorates intracerebral hemorrhage-induced inflammatory injury by regulating TRAF6 polyubiquitination

Meng Zhaoyou, Ting Zhao, Kai Zhou, Zhong Qi, Wang Yanchun, Xiong Xiaoyi, Wang Faxiang, Yang Yuanrui, Zhu Wenyao, Liu Juan, Liao Maofan, Lirong Wu, Duan Chunmei, Jie Li, Gong Qiuwen, Liu Liang, Xiong Ao, Yang Meihua, Wang Jian, Yang Qingwu

Research output: Contribution to journalArticlepeer-review

Abstract

Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A202/2 and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A202/2 and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A202/2 parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICHinduced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A202/2 parabionts compared with A202/2 mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A202/2 mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IkBa degradation and NF-kB activation were observed in A202/2 mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH.

Original languageEnglish (US)
Pages (from-to)820-831
Number of pages12
JournalJournal of Immunology
Volume198
Issue number2
DOIs
StatePublished - Jan 15 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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