DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke.

Abstract:

BACKGROUND: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. 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 I/R 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 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. CONCLUSION: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.

journal_name

J Neuroinflammation

authors

Peng L,Zhou Y,Jiang N,Wang T,Zhu J,Chen Y,Li L,Zhang J,Yu S,Zhao Y

doi

10.1186/s12974-020-01764-x

subject

Has Abstract

pub_date

2020-03-09 00:00:00

pages

81

issue

1

issn

1742-2094

pii

10.1186/s12974-020-01764-x

journal_volume

17

pub_type

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