TY - JOUR
T1 - A20 ameliorates intracerebral hemorrhage-induced inflammatory injury by regulating TRAF6 polyubiquitination
AU - Zhaoyou, Meng
AU - Zhao, Ting
AU - Zhou, Kai
AU - Qi, Zhong
AU - Yanchun, Wang
AU - Xiaoyi, Xiong
AU - Faxiang, Wang
AU - Yuanrui, Yang
AU - Wenyao, Zhu
AU - Juan, Liu
AU - Maofan, Liao
AU - Wu, Lirong
AU - Chunmei, Duan
AU - Li, Jie
AU - Qiuwen, Gong
AU - Liang, Liu
AU - Ao, Xiong
AU - Meihua, Yang
AU - Jian, Wang
AU - Qingwu, Yang
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2017/1/15
Y1 - 2017/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014728096&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014728096&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1600334
DO - 10.4049/jimmunol.1600334
M3 - Article
C2 - 27986908
AN - SCOPUS:85014728096
SN - 0022-1767
VL - 198
SP - 820
EP - 831
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -