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Initiation and perpetuation of NLRP 3 inflammasome activation and assembly

Initiation and perpetuation of NLRP 3 inflammasome activation and assembly Summary The NLRP3 (NOD‐like receptor family, pyrin domain containing 3) inflammasome is a multiprotein complex that orchestrates innate immune responses to infection and cell stress through activation of caspase‐1 and maturation of inflammatory cytokines pro‐interleukin‐1β (pro‐IL‐1β) and pro‐IL‐18. Activation of the inflammasome during infection can be protective, but unregulated NLRP3 inflammasome activation in response to non‐pathogenic endogenous or exogenous stimuli can lead to unintended pathology. NLRP3 associates with mitochondria and mitochondrial molecules, and activation of the NLRP3 inflammasome in response to diverse stimuli requires cation flux, mitochondrial Ca2+ uptake, and mitochondrial reactive oxygen species accumulation. It remains uncertain whether NLRP3 surveys mitochondrial integrity and senses mitochondrial damage, or whether mitochondria simply serve as a physical platform for inflammasome assembly. The structure of the active, caspase‐1‐processing NLRP3 inflammasome also requires further clarification, but recent studies describing the prion‐like properties of ASC have advanced the understanding of how inflammasome assembly and caspase‐1 activation occur while raising new questions regarding the propagation and resolution of NLRP3 inflammasome activation. Here, we review the mechanisms and pathways regulating NLRP3 inflammasome activation, discuss emerging concepts in NLRP3 complex organization, and expose the knowledge gaps hindering a comprehensive understanding of NLRP3 activation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Immunological Reviews Wiley

Initiation and perpetuation of NLRP 3 inflammasome activation and assembly

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References (193)

Publisher
Wiley
Copyright
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
ISSN
0105-2896
eISSN
1600-065X
DOI
10.1111/imr.12286
pmid
25879282
Publisher site
See Article on Publisher Site

Abstract

Summary The NLRP3 (NOD‐like receptor family, pyrin domain containing 3) inflammasome is a multiprotein complex that orchestrates innate immune responses to infection and cell stress through activation of caspase‐1 and maturation of inflammatory cytokines pro‐interleukin‐1β (pro‐IL‐1β) and pro‐IL‐18. Activation of the inflammasome during infection can be protective, but unregulated NLRP3 inflammasome activation in response to non‐pathogenic endogenous or exogenous stimuli can lead to unintended pathology. NLRP3 associates with mitochondria and mitochondrial molecules, and activation of the NLRP3 inflammasome in response to diverse stimuli requires cation flux, mitochondrial Ca2+ uptake, and mitochondrial reactive oxygen species accumulation. It remains uncertain whether NLRP3 surveys mitochondrial integrity and senses mitochondrial damage, or whether mitochondria simply serve as a physical platform for inflammasome assembly. The structure of the active, caspase‐1‐processing NLRP3 inflammasome also requires further clarification, but recent studies describing the prion‐like properties of ASC have advanced the understanding of how inflammasome assembly and caspase‐1 activation occur while raising new questions regarding the propagation and resolution of NLRP3 inflammasome activation. Here, we review the mechanisms and pathways regulating NLRP3 inflammasome activation, discuss emerging concepts in NLRP3 complex organization, and expose the knowledge gaps hindering a comprehensive understanding of NLRP3 activation.

Journal

Immunological Reviews – Wiley

Published: May 1, 2015

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