The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Gout-associated uric acid crystals activate the NALP3 inflammasome
Abstract
Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.
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In the citing paper
“Colchicine impairs neutrophil adhesion to vascular endothelium and degranulation and blocks activation of the NLRP3 (NOD-, LRR-, and pyrin domaincontaining protein 3) inflammasome, which is required for cleaving caspase-1 leading to the production of IL-1 β and IL-18. 134-136”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [135]
In the citing paper
“Nucleotide products such as uric acid can also function as DAMPs, presumably by activating the inflammasome in APC, thereby stimulating the production of inflammatory cytokines such as interleukin-1β (IL-1β), IL-18 and IL-33, the secretion of which depends on the inflammasome-mediated activation of caspase-145,46.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [46]
In the citing paper
“The secretion of mature IL-1β induced by asbestos was comparable to amounts observed with monosodium urate crystals (MSU), a known potent activator of IL-1β processing (7) (Fig. 1, A and B).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [7]
In the citing paper
“In addition to PAMPs, Nalp3 has the extraordinary capacity of sensing endogenous stress-associated danger signals (DAMPs) such as ATP (9) or MSU (7).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [7]
In the citing paper
“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).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [7]
In the citing paper
“The NLRP3 inflammasome senses crystalline danger signals that can occur during autoinflammatory diseases, such as gout or atherosclerosis, and environmental diseases, such as silicosis or asbestosis (18, 20, 22).”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [18]
In the citing paper
“Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inflammasome, a cytosolic receptor complex that plays a critical role in driving inflammatory immune responses.”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [18]
In the citing paper
“NLRP3 has been shown to respond to sterile stimuli, including asbestos, silica, MSU and CPPD crystals55, cholesterol crystals and β-amyloid fibrils56.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [55]
In the citing paper
“Urate and cholesterol crystals, as well as sterile particulates, for example, can bypass the requirement for ATP and P2RX7 for IL-1β production55,59.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [55]
In the citing paper
“Consistently, in mouse models of sterile injury, such as gout, asbestosis and silicosis, NLRP3-deficient mice exhibited decreased inflammation with reduced levels of tissue infiltration by neutrophils or macrophages55,57,58.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [55]
In the citing paper
“The inflammasome is a multimolecular cytosolic sensor that detects pathogenic microorganisms and sterile stressors and activates caspase-1 during the process of pyroptosis, which, in turn, causes the inactive precursor forms of interleukin-1β and interleukin-18 to become the active forms.”
From Cytokine storm (2020) · cites this paper as [41]
Citations
Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
Self-citationThe Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205
Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
Mariathasan, S., Newton, K., Monack, D. M., Vucic, D., French, D. M., Lee, W. P., Roose-Girma, M., Erickson, S. L., & Dixit, V. M. (2004) · Nature · doi:10.1038/nature02664 · Cited by 1,864
Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., & Tschopp, J. (2004) · Immunity · doi:10.1016/s1074-7613(04)00046-9 · Cited by 1,768
Self-citationMolecular identification of a danger signal that alerts the immune system to dying cells
Shi, Y., Evans, J. E., & Rock, K. L. (2003) · Nature · doi:10.1038/nature01991 · Cited by 1,684
Hoffman, H. M., Mueller, J. L., Broide, D. H., Wanderer, A. A., & Kolodner, R. D. (2001) · Nature Genetics · doi:10.1038/ng756 · Cited by 1,679
Martinon, F., & Tschopp, J. (2004) · Cell · doi:10.1016/j.cell.2004.05.004 · Cited by 957
Self-citationNALPs: a novel protein family involved in inflammation
Tschopp, J., Martinon, F., & Burns, K. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1019 · Cited by 739
Self-citationNLRs join TLRs as innate sensors of pathogens
Martinon, F., & Tschopp, J. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.06.004 · Cited by 673
Self-citationInterleukin-1–Receptor Antagonist in the Muckle–Wells Syndrome
Hawkins, P. N., Lachmann, H. J., & McDermott, M. F. (2003) · New England Journal of Medicine · doi:10.1056/nejm200306193482523 · Cited by 654
Identification of Bacterial Muramyl Dipeptide as Activator of the NALP3/Cryopyrin Inflammasome
Martinon, F., Agostini, L., Meylan, E., & Tschopp, J. (2004) · Current Biology · doi:10.1016/j.cub.2004.10.027 · Cited by 579
Self-citationHoffman, H. M., Rosengren, S., Boyle, D. L., Cho, J. Y., Nayar, J., Mueller, J. L., Anderson, J. P., Wanderer, A. A., & Firestein, G. S. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17401-1 · Cited by 552
Blocking IL-1 in systemic inflammation
Dinarello, C. A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050640 · Cited by 501
Shoham, N. G., Centola, M. B., Mansfield, E. A., Hull, K. M., Wood, G., Wise, C. A., & Kastner, D. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135380100 · Cited by 497
Liu‐Bryan, R., Scott, P., Sydlaske, A., Rose, D. M., & Terkeltaub, R. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21238 · Cited by 414
Chae, J. J., Komarow, H. D., Cheng, J., Wood, G., Raben, N., Liu, P. P., & Kastner, D. L. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00056-x · Cited by 412
Familial autoinflammatory diseases: genetics, pathogenesis and treatment
STOJANOV, S., & Kastner, D. L. (2005) · Current Opinion in Rheumatology · doi:10.1097/bor.0000174210.78449.6b · Cited by 348
ACUTE ARTHRITIS IN MAN AND DOG AFTER INTRASYNOVIAL INJECTION OF SODIUM URATE CRYSTALS
Faires, J. S., & McCarty, D. J. (1962) · The Lancet · doi:10.1016/s0140-6736(62)90501-9 · Cited by 270
TNFRSF1A mutations and autoinflammatory syndromes
Galon, J., Aksentijevich, I. A., McDermott, M., O’Shea, J. J., & Kastner, D. L. (2000) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00124-2 · Cited by 240
Update on colchicine and its mechanism of action
Molad, Y. (2002) · Current Rheumatology Reports · doi:10.1007/s11926-002-0073-2 · Cited by 213
Mechanisms of inflammation in gout
Dalbeth, N., & Haskard, D. O. (2005) · Lara D. Veeken · doi:10.1093/rheumatology/keh640 · Cited by 211
Yamamoto, M., Yaginuma, K., Tsutsui, H., Sagara, J., Guan, X., Seki, E., Yasuda, K., Yamamoto, M., Akira, S., Nakanishi, K., et al. (2004) · Genes to Cells · doi:10.1111/j.1365-2443.2004.00789.x · Cited by 184
New insights into the mechanism of IL-1β maturation
Burns, K., Martinon, F., & Tschopp, J. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00017-1 · Cited by 143
Self-citationChapman, P. T., Yarwood, H., Harrison, A. A., Stocker, C. J., Jamar, F., Gundel, R. H., Peters, A. M., & Haskard, D. O. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780400525 · Cited by 99
Getting, S. J., Flower, R. J., Parente, L., de Médicis, R., Lussier, A., Woliztky, B. A., Martins, M. A., & Perretti, M. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37005-3 · Cited by 90
Suppression of metabolic accompaniments of phagocytosis by colchicine
Goldfinger, S. E., Howell, R. R., & Seegmiller, J. E. (1965) · Arthritis & Rheumatism · doi:10.1002/art.1780080610 · Cited by 57
The Effect of Pretreatment with Colchicine on the Inflammatory Response to Microcrystalline Urate
Malawista, S. E., & SEEGMILLER, J. E. (1965) · Annals of Internal Medicine · doi:10.7326/0003-4819-62-4-648 · Cited by 54
XVII. On gouty and urinary concretions
Wollaston, W. H. (1797) · Philosophical Transactions of the Royal Society of London · doi:10.1098/rstl.1797.0019 · Cited by 51
Padgett, J. J. (1994) · Journal of Psychosocial Nursing and Mental Health Services · doi:10.3928/0279-3695-19940101-04 · Cited by 47
Meng, Z. H., Hudson, A. P., Schumacher, H. R., Baker, J. F., & Baker, D. G. (1997) · PubMed · Cited by 47
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Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
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Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
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Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
Metadata
- Authors
- Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J.
- Affiliations
- University of Lausanne (CH)
- Corresponding author
- Tschopp, Jürg
- Venue
- Nature
- Published
- 2006-01-11
- Volume
- 440
- Issue
- 7081
- Pages
- 237-241
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2009800174
- Cited by
- 5,326
- References
- 31
- Citations by year
- 2026: 227 · 2025: 246 · 2024: 305 · 2023: 310 · 2022: 333 · 2021: 335 · 2020: 340 · 2019: 297 · 2018: 280 · 2017: 248 · 2016: 287 · 2015: 290 · 2014: 271 · 2013: 299 · 2012: 238
- FWCI
- 76.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NLRP3 inflammasome, NLRP3, gout, urate crystals, monosodium urate, calcium pyrophosphate dihydrate, pseudogout, caspase-1, IL-1β, IL-18, autoinflammatory disease, innate immunity, crystal-induced inflammation, neutrophil influx, IL-1 receptor, macrophages
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Calcium Pyrophosphate, Carrier Proteins, Cell Line, Cells, Cultured, Chondrocalcinosis, Colchicine, Disease Models, Animal, Gout, Humans, Inflammation, Interleukin-1, Macrophages, Neutrophils, Peritonitis, Uric Acid, Receptors, Interleukin-1, Caspase 1, Mice
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