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The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response
Open accessAbstract
Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.
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“They can also be recognized by neighboring microglia as a danger signal and induce inflammatory responses including activation of the NLRP3 inflammasome, thereby propagating inflammation [70–72].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [71]
In the citing paper
“In turn, NLRP3 inflammasome activity leads to the extracellular release of ASC particles that may function as danger signals (246).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [246]
In the citing paper
“Increased expression and activity of the NLRP3 inflammasome machinery in circulating immune cells of patients affected by depression (245), bipolar disorder (246), and ASD (226), have been reported.”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [246]
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Metadata
- Authors
- Baroja-Mazo, A., Martín-Sánchez, F., Gomez, A. I., Martínez, C. M., Amores-Iniesta, J., Compan, V., Barberà-Cremades, M., Yagüe, J., Ruiz-Ortiz, E., Antón, J., Buján, S., Couillin, I., Brough, D., Arostegui, J. I., & Pelegrín, P.
- Affiliations
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- University of Manchester (GB)
- Hospital Clínic de Barcelona (ES)
- Hospital Sant Joan de Déu Barcelona (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Université d'Orléans (FR)
- ORCID
- Venue
- Nature Immunology
- Published
- 2014-06-22
- Volume
- 15
- Issue
- 8
- Pages
- 738-748
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2143119237
- Cited by
- 790
- References
- 50
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 41 · 2023: 63 · 2022: 81 · 2021: 84 · 2020: 86 · 2019: 68 · 2018: 74 · 2017: 88 · 2016: 60 · 2015: 57 · 2014: 20
- FWCI
- 30.77
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- 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 inflammasome, caspase-1, IL-1β processing, cryopyrin-associated periodic syndromes, macrophages, autoinflammatory disease, phagocytosis
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Humans, Inflammation, Macrophages, Mice, Inbred C57BL, Phagocytosis, Signal Transduction, Mice, Knockout, Caspases, Caspase 1, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins, Caspases, Initiator, Interleukin-1beta, Cryopyrin-Associated Periodic Syndromes, HEK293 Cells, Inflammasomes
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