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The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA
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Int. J. Mol. Sci. 2019, 20(13), 3328; https://doi.org/10.3390/ijms20133328
Received: 31 May 2019 / Revised: 1 July 2019 / Accepted: 3 July 2019 / Published: 6 July 2019
(This article belongs to the Special Issue Cytoplasmic Sensors: Infection, Inflammation, and Immunity)
The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3. View Full-Text
Keywords: NLRP3 inflammasome; Priming; Ionic flux; ROS; Mitochondrial dysfunction; Lysosomal damage; Post-translational modification; NLRP3 regulators NLRP3 inflammasome; Priming; Ionic flux; ROS; Mitochondrial dysfunction; Lysosomal damage; Post-translational modification; NLRP3 regulators
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Kelley, N.; Jeltema, D.; Duan, Y.; He, Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019, 20, 3328.

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