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Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion

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Abstract

Objective

Current therapies for ischemia/reperfusion are insufficient because of our poor understanding of the mechanisms of brain injury after ischemic stroke. As a vital component of the innate immune system, NLRP3 inflammasome contributes to ischemic brain injury; however, a detailed understanding of their molecular mechanisms is unknown. This study was designed to investigate the effect of nuclear factor E2-related factor-2 (Nrf2) on NLRP3 inflammasome.

Materials and methods

BV2 microglial cells were pretreated with tert-butylhydroquinone or Nrf2 CRISPR plasmid before oxygen–glucose deprivation/reoxygenation (OGDR) exposure. Then we observed the effect of Nrf2 on NLRP3 inflammasome.

Results

We identified that Nrf2 activation inhibited NLRP3 inflammasome expression and subsequent IL-1β generation. Furthermore, the activation of NLRP3 inflammasome was sensitive to the reactive oxygen species (ROS) level and Nrf2 could decrease the production of ROS. Additionally, as a Nrf2-targeted ARE gene, NADPH quinone oxidoreductase 1 was involved in the inhibition of the NLRP3 inflammasome.

Conclusion

We elucidated an inhibitory regulation of Nrf2/ARE pathway on ROS-induced NLRP3 inflammasome activation in BV2 microglial cells after OGDR exposure.

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Author information

Author notes

  1. Xiujian Xu and Liang Zhang are co-first authors.

Authors and Affiliations

  1. Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, Jiangsu, China

    Xiujian Xu & Ming Yu

  2. Xuzhou Medical University, Xuzhou, Jiangsu, China

    Liang Zhang, Qi Hao & Tao Zhang

  3. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221006, Jiangsu, China

    Xinchun Ye & Guiyun Cui

Authors
  1. Xiujian Xu
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  2. Liang Zhang
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  4. Qi Hao
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  5. Tao Zhang
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  6. Guiyun Cui
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  7. Ming Yu
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Corresponding authors

Correspondence to Guiyun Cui or Ming Yu.

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Sources of funding

This work was supported by the National Natural Science Foundation of China (Nos. 81571155 and 81571210).

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The authors declare that there is no conflict of interest regarding the publication of this paper.

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Responsible Editor: John Di Battista.

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Xu, X., Zhang, L., Ye, X. et al. Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion. Inflamm. Res. 67, 57–65 (2018). https://doi.org/10.1007/s00011-017-1095-6

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  • DOI: https://doi.org/10.1007/s00011-017-1095-6

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