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The Inflammasome
Open accessAbstract
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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In the citing paper
“Mature IL-1β is produced by cleavage of the inactive proIL-1β precursor by caspase-1, which is activated within a large multi-protein complex, termed the inflammasome (8).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [8]
In the citing paper
“The Nalp3 inflammasome, composed of the Nod-like receptor (NLR) protein Nalp3 (Cryopyrin/NLRP3), Cardinal, the adaptor ASC and caspase-1, is implicated in the production of mature IL-1β in response to a variety of signals.”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [8]
In the citing paper
“Caspase-1 belongs to the inflammatory caspases and leads to the processing and secretion of the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and IL-18 into their active forms (21).”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [21]
In the citing paper
“Among the different types of PRRs, the newest described is the inflammasome, a high-molecular-weight complex, present in the cytosol of immune cells [132].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [132]
In the citing paper
“Caspase-1 is also regulated in a similar manner and requires cleavage from pro-caspase-1.This occurs via the formation of a multimeric protein complex termed the inflammasome.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Martinon et al, 2002
In the citing paper
“IL-1β is transcribed into the precursor protein pro-IL-1β and requires enzymatic cleavage by caspase-1 into the bioactive and mature IL-1β.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Martinon et al, 2002
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“A newly identified PRR, first described in detail in 2002, is the inflammasome (Martinon et al., 2002; Gentile et al., 2015; Jorgensen and Miao, 2015; Sanders et al., 2015).”
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Metadata
- 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)
- 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
- 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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