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The Signaling Pathways Regulating NLRP3 Inflammasome Activation

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Abstract

The NLRP3 inflammasome is a multi-molecular complex that acts as a molecular platform to mediate caspase-1 activation, leading to IL-1β/IL-18 maturation and release in cells stimulated by various pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). This inflammasome plays an important role in the innate immunity as its activation can further promote the occurrence of inflammation, enhance the ability of host to remove pathogens, and thus facilitate the repair of injured tissues. But if the inflammasome activation is dysregulated, it will cause the development of various inflammatory diseases and metabolic disorders. Therefore, under normal conditions, the activation of inflammasome is tightly regulated by various positive and negative signaling pathways to respond to the stimuli without damaging the host itself while maintaining homeostasis. In this review, we summarize recent advances in the major signaling pathways (including TLRs, MAPK, mTOR, autophagy, PKA, AMPK, and IFNR) that regulate NLRP3 inflammasome activation, providing a brief view of the molecular network that regulates this inflammasome as a theoretical basis for therapeutic intervention of NLRP3 dysregulation-related diseases.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81873064, No. 81773965 and No. 81673664).

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  1. Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China

    Ming-ye Chen, Xun-jia Ye, Xian-hui He & Dong-yun Ouyang

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Chen M and Ye X wrote this manuscript. He X and Ouyang D conceived and supervised this review.

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Chen, My., Ye, Xj., He, Xh. et al. The Signaling Pathways Regulating NLRP3 Inflammasome Activation. Inflammation 44, 1229–1245 (2021). https://doi.org/10.1007/s10753-021-01439-6

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