Cited by 830Inflammasome and immune disordersImmune Response and InflammationIL-33, ST2, and ILC Pathways

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Initiation and perpetuation of NLRP 3 inflammasome activation and assembly

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Elliott, Eric I., Sutterwala, Fayyaz S.·2015·Immunological Reviews

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Abstract

Summary: The NLRP 3 ( 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 NLRP 3 inflammasome activation in response to non‐pathogenic endogenous or exogenous stimuli can lead to unintended pathology. NLRP 3 associates with mitochondria and mitochondrial molecules, and activation of the NLRP 3 inflammasome in response to diverse stimuli requires cation flux, mitochondrial Ca 2+ uptake, and mitochondrial reactive oxygen species accumulation. It remains uncertain whether NLRP 3 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 NLRP 3 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 NLRP 3 inflammasome activation. Here, we review the mechanisms and pathways regulating NLRP 3 inflammasome activation, discuss emerging concepts in NLRP 3 complex organization, and expose the knowledge gaps hindering a comprehensive understanding of NLRP 3 activation.

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Authors: Elliott, E. I., & Sutterwala, F. S.
Affiliations: University of Iowa (US)
Corresponding author: Sutterwala, Fayyaz S.
ORCID: Elliott, Eric I.
Sutterwala, Fayyaz S.
Venue: Immunological Reviews
Publisher: Wiley
Published: 2015-04-16
Volume: 265
Issue: 1
Pages: 35-52
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/imr.12286
PMC: PMC4400874
OpenAlex: W2068633454
Cited by: 821
References: 186
Citations by year: 2026: 39 · 2025: 56 · 2024: 87 · 2023: 93 · 2022: 127 · 2021: 98 · 2020: 87 · 2019: 79 · 2018: 63 · 2017: 43 · 2016: 37 · 2015: 11
FWCI: 4.98
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunological Reviews (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R01 AI087630, T32 GM007337)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: NLRP3 inflammasome, inflammasome assembly, caspase-1 activation, mitochondrial calcium uptake, mitochondrial reactive oxygen species, innate immunity
MeSH terms: NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Humans, Immunity, Innate, Mitochondria, Calcium Signaling, Caspase 1, Multiprotein Complexes, Inflammasomes

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Initiation and perpetuation of NLRP 3 inflammasome activation and assembly

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