Acute inflammation induced by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important for protecting the resultant lesion. Our previous study demonstrated that DJ-1 is abundantly expressed in reactive astrocytes after cerebral I/R injury. Here, we show that DJ-1 negatively regulates the inflammatory response by facilitating the interaction between SHP-1 and TRAF6, thereby inducing the dissociation of NLRX1 from TRAF6. We used oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro in primary astrocyte cultures and transient middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to mimic I/R insult. The inhibition of DJ-1 expression increased the expression of the inflammatory cytokines TNF-α, IL-1β, and IL-6. DJ-1 knockdown facilitated the interaction between NLRX1 and TRAF6. However, the loss of DJ-1 attenuated the interaction between SHP-1 and TRAF6. In subsequent experiments, a SHP-1 inhibitor altered the interaction between SHP-1 and TRAF6 and facilitated the interaction between NLRX1 and TRAF6 in DJ-1-overexpressing astrocytes. These findings suggest that DJ-1 exerts an SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 from TRAF6 during cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.

中文翻译：

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DJ-1在卒中中发挥抗炎作用并通过SHP-1调节NLRX1-TRAF6

脑缺血/再灌注（I / R）损伤后由反应性星形胶质细胞诱导的急性炎症对于保护所得病变非常重要。我们之前的研究表明，DJ-1在脑I / R损伤后在反应性星形胶质细胞中大量表达。在这里，我们显示DJ-1通过促进SHP-1和TRAF6之间的相互作用负调节炎症反应，从而诱导NLRX1从TRAF6上解离。我们在体外原代星形胶质细胞培养中使用了氧葡萄糖剥夺/复氧（OGD / R），并在体内使用了短暂的大脑中动脉闭塞/再灌注（MCAO / R）来模拟I / R损伤。DJ-1表达的抑制增加了炎性细胞因子TNF-α，IL-1β和IL-6的表达。DJ-1组合式促进了NLRX1和TRAF6之间的相互作用。然而，DJ-1的丢失减弱了SHP-1与TRAF6之间的相互作用。在随后的实验中，SHP-1抑制剂改变了SHP-1和TRAF6之间的相互作用，并促进了过表达DJ-1的星形胶质细胞中NLRX1和TRAF6之间的相互作用。这些发现表明，DJ-1在脑I / R损伤中发挥SHP-1依赖性的抗炎作用，并诱导TRAX6从NLRX1分离。因此，DJ-1可能是治疗I / R损伤的有效治疗靶标。这些发现表明，DJ-1在脑I / R损伤中发挥SHP-1依赖性的抗炎作用，并诱导TRAX6从NLRX1分离。因此，DJ-1可能是治疗I / R损伤的有效治疗靶标。这些发现表明，DJ-1在脑I / R损伤中发挥SHP-1依赖性的抗炎作用，并诱导TRAX6从NLRX1分离。因此，DJ-1可能是治疗I / R损伤的有效治疗靶标。