Cited by 1,768Inflammasome and immune disordersImmune Response and InflammationAutoimmune and Inflammatory Disorders Research

NALP3 Forms an IL-1β-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder

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Agostini, Laetitia, Martinon, Fabio, Burns, Kimberly, McDermott, Michael F., Hawkins, Philip N., Tschopp, Jürg·2004·Immunity

Abstract

Mutations within the NALP3/cryopyrin/CIAS1 gene are responsible for three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. The NALP3 protein is homologous to NALP1, which is a component of the inflammasome, a molecular platform that activates the proinflammatory caspases-1 and -5. NALP3 (and other members of the NALP family) lacks the C-terminal, CARD-containing sequence of NALP1, and its role in caspase activation is unclear. Here, we report that NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity. Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders.

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Crossref · 10.1016/s1074-7613(04)00046-9

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  • The Nalp3 inflammasome has been linked to excessive IL-1β in autoinflammatory conditions like Muckle-Wells syndrome and in inflammatory diseases such as gout and pseudogout.

    “The Nalp3 inflammasome is implicated in the pathological increase of IL-1β production in autoinflammatory syndromes, such as Muckle-Wells syndrome (22), as well as inflammatory processes, such as gout and pseudogout (7).”

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Authors
Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., & Tschopp, J.
Affiliations
  • University of Lausanne (CH)
  • Queen Mary University of London (GB)
  • The Royal Free Hospital (GB)
Corresponding author
Tschopp, Jürg
Venue
Immunity
Publisher
Elsevier BV
Published
2004-03
Volume
20
Issue
3
Pages
319-325
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2134735862
Cited by
1,768
References
28
Citations by year
2026: 44 · 2025: 70 · 2024: 66 · 2023: 73 · 2022: 97 · 2021: 74 · 2020: 90 · 2019: 90 · 2018: 61 · 2017: 84 · 2016: 70 · 2015: 101 · 2014: 102 · 2013: 106 · 2012: 88
FWCI
24.21
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
NLRP3, Muckle-Wells syndrome, autoinflammatory disease, inflammasome, IL-1β processing, caspase-1, caspase-5, ASC, macrophages, familial cold autoinflammatory syndrome, CINCA, CARD domain, innate immunity
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Autoimmune Diseases, Carrier Proteins, Cell Line, Cells, Cultured, Cytoskeletal Proteins, Humans, Inflammation, Interleukin-1, Macrophages, Mutation, Neoplasm Proteins, Protein Precursors, Protein Structure, Tertiary, Caspase 1, Macromolecular Substances, Adaptor Proteins, Signal Transducing, CARD Signaling Adaptor Proteins

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