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

Journal of Neuroinflammation
Li PengYong Zhao

Abstract

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. Th...Continue Reading

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Citations

Apr 25, 2020·International Journal of Molecular Sciences·John BrownCesar V Borlongan
Oct 18, 2020·Biomedicines·Maria EjmaGjumrakch Aliev
Dec 15, 2020·Immunology·Robert J Pickering, Lee M Booty
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Tingting WangYong Zhao
Feb 3, 2021·International Journal of Molecular Sciences·Tünde FeketeKitti Pázmándi
Dec 22, 2020·Frontiers in Cellular and Infection Microbiology·Tiia Snäkä, Nicolas Fasel
Feb 10, 2021·Redox Biology·Federica De LazzariMarco Bisaglia

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
transfection
immunoprecipitation
ELISA
deubiquitination

Software Mentioned

GraphPad Prism
ImageJ

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