Cited by 6,066Inflammasome and immune disordersImmune Response and InflammationCell death mechanisms and regulation

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The Inflammasome

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Martinon, Fabio, Burns, Kimberly, Tschopp, Jürg·2002·Molecular Cell

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Abstract

Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.

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Authors: Martinon, F., Burns, K., & Tschopp, J.
Affiliations: University of Lausanne (CH)
Corresponding author: Tschopp, Jürg
ORCID: Martinon, Fabio
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2002-08
Volume: 10
Issue: 2
Pages: 417-426
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(02)00599-3
OpenAlex: W1529674879
Cited by: 6,066
References: 49
Citations by year: 2026: 260 · 2025: 343 · 2024: 431 · 2023: 450 · 2022: 466 · 2021: 417 · 2020: 457 · 2019: 397 · 2018: 315 · 2017: 315 · 2016: 285 · 2015: 300 · 2014: 256 · 2013: 230 · 2012: 200
FWCI: 16.27
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4003 d)
Locations: Molecular Cell (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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: inflammasome, caspase-1, caspase-5, PYCARD, ASC, NALP1, interleukin-1β processing, caspase activation, innate immunity, pyrin domain, THP-1 cells, lipopolysaccharide, dominant-negative mutant
MeSH terms: NLR Proteins, Cell Line, Cell-Free System, Cytoskeletal Proteins, Enzyme Activation, HeLa Cells, Humans, Inflammation, Interleukin-1, Lipopolysaccharides, Protein Precursors, Protein Processing, Post-Translational, Proteins, Blotting, Western, Caspases, Caspase 1, Macromolecular Substances, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, CARD Signaling Adaptor Proteins

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