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Crosstalk between ER stress, NLRP3 inflammasome, and inflammation

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Abstract

Endoplasmic reticulum stress (ERS) is a protective response to restore protein homeostasis by activating the unfolded protein response (UPR). However, UPR can trigger cell death under severe and/or persistently high ERS. The NLRP3 inflammasome is a complex of multiple proteins that activates the secretion of the proinflammatory cytokine IL-1β in a caspase-1-dependent manner to participate in the regulation of inflammation. The NLRP3 inflammasome involvement in ERS-induced inflammation has not been completely described. The intersection of ERS with multiple inflammatory pathways can initiate and aggravate chronic diseases. Accumulating evidence suggests that ERS-induced activation of NLRP3 inflammasome is the pathological basis of various inflammatory diseases. In this review, we have discussed the networks between ERS and NLRP3 inflammasome, with the view to identifying novel therapeutic targets in inflammatory diseases.

Key points

Endoplasmic reticulum stress (ERS) is an important factor for the activation of the NLRP3 inflammasomes that results in pathological processes.

ERS can activate the NLRP3 inflammasome to induce inflammatory responses via oxidative stress, calcium homeostasis, and NF-κB activation.

The interactions between ERS and NLRP3 inflammasome are associated with inflammation, which represent a potential therapeutic opportunity of inflammatory diseases.

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Acknowledgments

Thanks to everyone who helped me in the past three years, and thank my boyfriend to accompany me through those difficult times.

Funding

This study was supported by the National Natural Science Foundation of China (No 81201331) and Major special projects of the Hunan Provincial Health and Family Planning Commission (A2017011).

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Wrote the paper: Wei Li and Ting Cao. Revised the paper: Chunyi Luo, Xiangping Zhou, and Jialun Jia. Critically revised the manuscript for important intellectual content: Xinhua Xiao and Shuangquan Liu. All authors read and approved the final manuscript.

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Correspondence to Xinhua Xiao or Shuangquan Liu.

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The authors declare that they have no competing interests.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Li, W., Cao, T., Luo, C. et al. Crosstalk between ER stress, NLRP3 inflammasome, and inflammation. Appl Microbiol Biotechnol 104, 6129–6140 (2020). https://doi.org/10.1007/s00253-020-10614-y

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  • DOI: https://doi.org/10.1007/s00253-020-10614-y

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