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

Li, Peng; Zhou, Yang; Jiang, Ning; Wang, Tingting; Zhu, Jing; Chen, Yanlin; Li, Linyu; Zhang, Jinyan; Yu, Shanshan; Zhao, Yong

doi:10.1186/s12974-020-01764-x

Cited by 42 publications

(28 citation statements)

References 43 publications

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“…Then dehydrated with increasing concentrations of alcohol. After transparentized by xylene for 3 min, sealed with neutral resin ( Peng et al, 2020 ). All the sections were assessed the pathological changes by a microscope.…”

Section: Methodsmentioning

confidence: 99%

“…As a multifunctional protein, DJ-1 is involved in a variety of signal transduction pathways, including those associated with antioxidative stress, free radical scavenging and mitochondrial homeostasis ( Repici and Giorgini, 2019 ). Our previous study showed that DJ-1 negatively regulated cerebral I/R inflammatory responses by promoting SHP-1 and TRAF6 interactions ( Peng et al, 2020 ). Researchers hypothesized that DJ-1-deficient microglia exhibited increased cytotoxicity by promoting the secretion of the proinflammatory cytokines IL-1β and IL-6 ( Trudler et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion

Wang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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The polarization of microglia/macrophage, the resident immune cells in the brain, plays an important role in the injury and repair associated with ischemia-reperfusion (I/R). Previous studies have shown that DJ-1 has a protective effect in cerebral I/R. We found that DJ-1 regulates the polarization of microglial cells/macrophages after cerebral I/R and explored the mechanism by which DJ-1 mediates microglial/macrophage polarization in cerebral I/R. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral I/R in vivo and in vitro, respectively. DJ-1 siRNA and the DJ-1-based polypeptide ND13 were used to produce an effect on DJ-1, and the P62-specific inhibitor XRK3F2 was used to block the effect of P62. Enhancing the expression of DJ-1 induced anti-inflammatory (M2) polarization of microglia/macrophage, and the expression of the anti-inflammatory factors IL-10 and IL-4 increased. Interference with DJ-1 expression induced pro-inflammatory (M1) polarization of microglia/macrophage, and the expression of the proinflammatory factors TNF-α and IL-1β increased. DJ-1 inhibited the expression of P62, impeded the interaction between P62 and TRAF6, and blocked nuclear entry of IRF5. In subsequent experiments, XRK3F2 synergistically promoted the effect of DJ-1 on microglial/macrophage polarization, further attenuating the interaction between P62 and TRAF6.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion

Wang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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“…The protective effect of NLRX1 in inflammation-associated diseases is also supported by a number of literature data. For example, NLRX1 alleviates hypoxia-induced apoptosis and inflammation during acute myocardial infarction [ 98 ], or acts as an anti-inflammatory agent in cerebral ischemia reperfusion injury via decreasing pro-inflammatory cytokine production [ 99 ]. Furthermore, NLRX1 deficiency leads to exacerbated LPS-induced heart injury by enhancing NF-κB and NLRP3 inflammasome activation [ 100 ].…”

Section: Discussionmentioning

confidence: 99%

Focusing on the Cell Type Specific Regulatory Actions of NLRX1

Fekete

Bencze

Bíró

et al. 2021

IJMS

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Cells utilize a diverse repertoire of cell surface and intracellular receptors to detect exogenous or endogenous danger signals and even the changes of their microenvironment. However, some cytosolic NOD-like receptors (NLR), including NLRX1, serve more functions than just being general pattern recognition receptors. The dynamic translocation between the cytosol and the mitochondria allows NLRX1 to interact with many molecules and thereby to control multiple cellular functions. As a regulatory NLR, NLRX1 fine-tunes inflammatory signaling cascades, regulates mitochondria-associated functions, and controls metabolism, autophagy and cell death. Nevertheless, literature data are inconsistent and often contradictory regarding its effects on individual cellular functions. One plausible explanation might be that the regulatory effects of NLRX1 are highly cell type specific and the features of NLRX1 mediated regulation might be determined by the unique functional activity or metabolic profile of the given cell type. Here we review the cell type specific actions of NLRX1 with a special focus on cells of the immune system. NLRX1 has already emerged as a potential therapeutic target in numerous immune-related diseases, thus we aim to highlight which regulatory properties of NLRX1 are manifested in disease-associated dominant immune cells that presumably offer promising therapeutic solutions to treat these disorders.

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“…One study had highlighted the protein DJ‐1 (PARK7 and GATD2) in regulating CNS inflammation by NF‐κB signalling 110,111 . Recently, Peng et al 112 discovered this DJ‐1‐mediated regulation of inflammation is dependent on NLRX1 and an interactor protein SHP1. The authors use an oxygen–glucose deprivation IR model in primary astrocytes, as well as an in vivo cerebral occlusion model to assess the relationship of DJ‐1, SHP1 and NLRX1.…”

Section: Nlrx1 In Diseasementioning

confidence: 99%