DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke
Abstract Background : Acute inflammation developed by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important in protecting the resultant lesion. Our previous study demonstrated the abundant expression of DJ-1 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 NLRX1 dissociation from TRAF6. Methods : 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 ischemic reperfusion insult. Results: 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 of NLRX1 with TRAF6. However, the loss of DJ-1 attenuated the interaction of SHP-1 with TRAF6. In subsequent experiments, a SHP-1 inhibitor altered the interaction of SHP-1 with TRAF6 and facilitated the interaction of NLRX1 with TRAF6 in DJ-1-overexpressing astrocytes. Conclusion: This finding suggests that DJ-1 exerts a SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 and TRAF6 in cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.