Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
Abstract
Inflammasomes are Nod-like receptor(NLR)- and caspase-1-containing cytoplasmic multiprotein complexes, which upon their assembly, process and activate the proinflammatory cytokines interleukin (IL)-1beta and IL-18. The inflammasomes harboring the NLR members NALP1, NALP3 and IPAF have been best characterized. While the IPAF inflammasome is activated by bacterial flagellin, activation of the NALP3 inflammasome is triggered not only by several microbial components, but also by a plethora of danger-associated host molecules such as uric acid. How NALP3 senses these chemically unrelated activators is not known. Here, we provide evidence that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K(+) efflux from cells. Low intracellular K(+) is also a requirement for NALP1 inflammasome activation by lethal toxin of Bacillus anthracis. In vitro, NALP inflammasome assembly and caspase-1 recruitment occurs spontaneously at K(+) concentrations below 90 mM, but is prevented at higher concentrations. Thus, low intracellular K(+) may be the least common trigger of NALP-inflammasome activation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Lowering intracellular K+ through efflux is required for Nalp3 activation by every known activator, including MSU.
“In favour of the latter assumption is the recent finding that potassium (K + ) efflux, lowering intracellular K + levels, is a requirement for Nalp3 inflammasome activation triggered by all known activators including MSU (13)(14)(15).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [13]
Published findings indicate that ROS help activate caspase-1 after ATP treatment and contribute to Nalp3 activation by MSU and R837.
“Recent data also suggest a role for ROS in activating caspase-1 upon ATP treatment (18) and in Nalp3 inflammasome activation by MSU and R837 (13).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [13]
Decreased K+ levels in the cytosolic microenvironment may lead to NLRP3 inflammasome assembly and activation through Nek7 binding, culminating in secretion of IL-1β and IL-18.
“Decreased K+ levels in the cytosolic microenvironment may lead to NLRP3 inflammasome assembly and activation through NIMA-related serine/threonine kinase 7 (Nek7) binding, which culminates in the secretion of inflammatory cytokines, such as IL-1β and IL-18 [151,152]”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [152]
Inhibition of K+ efflux by high extracellular K+ concentrations prevents NLRP3-dependent caspase 1 activation in response to ATP, asbestos, silica and MSU crystals.
“Consistently, inhibition of K+ efflux by high extracellular K+ concentrations prevents NLRP3-dependent caspase 1 activation in response to ATP, asbestos, silica and MSU crystals58,66.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [66]
Cites
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · see citing works
Self-citationGout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326 · see citing works
Self-citationThe innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., & Aderem, A. A. (2001) · Nature · doi:10.1038/35074106 · Cited by 3,605 · see citing works
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080 · see citing works
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 1,822 · see citing works
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 · see citing works
Self-citationBacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3
Kanneganti, T., Özören, N., Body–Malapel, M., Amer, A. O., Park, J., Franchi, L., Whitfield, J. R., Barchet, W., Colonna, M., Vandenabeele, P., et al. (2006) · Nature · doi:10.1038/nature04517 · Cited by 1,149 · see citing works
Franchi, L., Amer, A., Body-Malapel, M., Kanneganti, T.-D., Özören, N., Jagirdar, R., Inohara, N., Vandenabeele, P., Bertin, J., Coyle, A., et al. (2006) · Nature Immunology · doi:10.1038/ni1346 · Cited by 1,131 · see citing works
Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A. (2006) · Nature Immunology · doi:10.1038/ni1344 · Cited by 1,127 · see citing works
NOD-LRR PROTEINS: Role in Host-Microbial Interactions and Inflammatory Disease
Inohara, N., Chamaillard, M., McDonald, C., & Núñez, G. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133347 · Cited by 993 · see citing works
Sutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.02.004 · Cited by 980 · see citing works
Martinon, F., & Tschopp, J. (2004) · Cell · doi:10.1016/j.cell.2004.05.004 · Cited by 940 · see citing works
Self-citationNalp1b controls mouse macrophage susceptibility to anthrax lethal toxin
Boyden, E. D., & Dietrich, W. F. (2006) · Nature Genetics · doi:10.1038/ng1724 · Cited by 860 · see citing works
Inflammatory caspases and inflammasomes: master switches of inflammation
Martinon, F., & Tschopp, J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402038 · Cited by 821 · see citing works
Self-citationCruz, C. M., Rinna, A., Forman, H. J., Ventura, A. L. M., Persechini, P. M., & Ojcius, D. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608083200 · Cited by 786 · see citing works
Perregaux, D. G., & Gabel, C. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36591-2 · Cited by 760 · see citing works
Reconstituted NALP1 Inflammasome Reveals Two-Step Mechanism of Caspase-1 Activation
Faustin, B., Lartigue, L., Bruey, J., Luciano, F., Sergienko, E. A., Bailly‐Maitre, B., Volkmann, N., Hanein, D., Rouiller, I., & Reed, J. C. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.01.032 · Cited by 709 · see citing works
Kanneganti, T., Body–Malapel, M., Amer, A. O., Park, J., Whitfield, J. R., Franchi, L., Taraporewala, Z. F., Miller, D. J., Patton, J. T., Inohara, N., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607594200 · Cited by 706 · see citing works
NLRs 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 · see citing works
Self-citationIdentification 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 · see citing works
Self-citationThe PYRIN-CARD Protein ASC Is an Activating Adaptor for Caspase-1
Srinivasula, S. M., Poyet, J.-L., Razmara, M., Datta, P., Zhang, Z., & Alnemri, E. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200179200 · Cited by 573 · see citing works
Gurcel, L., Abrami, L., Girardin, S. E., Tschopp, J., & van der Goot, F. G. (2006) · Cell · doi:10.1016/j.cell.2006.07.033 · Cited by 508 · see citing works
Self-citationActivation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity
Watanabe, H., Gaide, O., Pétrilli, V., Martinon, F., Contassot, E., Roques, S., Kummer, J. A., Tschopp, J., & French, L. E. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700819 · Cited by 416 · see citing works
Wang, L., Manji, G. A., Grenier, J. M., Al-Garawi, A. A., Merriam, S., Lora, J. M., Geddes, B. J., Briskin, M., DiStefano, P. S., & Bertin, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203915200 · Cited by 371 · see citing works
Balagué, C., Lin, B., Alcon, C., Flottes, G., Malmström, S., Köhler, C., Neuhaus, G., Pelletier, G., Gaymard, F., & Roby, D. (2003) · The Plant Cell · doi:10.1105/tpc.006999 · Cited by 365 · see citing works
CATERPILLER: A Novel Gene Family Important in Immunity, Cell Death, and Diseases
Ting, J. P.-Y., & Davis, B. K. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115616 · Cited by 349 · see citing works
Papin, S., Cuenin, S., Agostini, L., Martinon, F., Werner, S., Beer, H., Grütter, C., Grütter, M. G., & Tschopp, J. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402142 · Cited by 313 · see citing works
Self-citationPelegrı́n, P., & Surprenant, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m610351200 · Cited by 301 · see citing works
Grenier, J. M., Wang, L., Manji, G. A., Huang, W.-J., Al-Garawi, A. A., Kelly, R., Carlson, A., Merriam, S., Lora, J. M., Briskin, M., et al. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03416-6 · Cited by 296 · see citing works
Potassium‐inhibited processing of IL‐1 beta in human monocytes.
Walev, I., Reske, K., Palmer, M., Valeva, A., & Bhakdi, S. C. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07149.x · Cited by 278 · see citing works
Physiological Concentrations of K+ Inhibit Cytochrome c-dependent Formation of the Apoptosome
Cain, K., Langlais, C., Sun, X.-M., Brown, D. G., & Cohen, G. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107419200 · Cited by 197 · see citing works
Tollip Regulates Proinflammatory Responses to Interleukin-1 and Lipopolysaccharide
Didierlaurent, A. M., Brissoni, B., Velin, D., Aebi, N., Tardivel, A., Käslin, E., Sirard, J., Angelov, G. S., Tschopp, J., & Burns, K. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.3.735-742.2006 · Cited by 195 · see citing works
Self-citationEngagement of CD14 Mediates the Inflammatory Potential of Monosodium Urate Crystals
Scott, P., Ma, H., Viriyakosol, S., Terkeltaub, R. A., & Liu‐Bryan, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.6370 · Cited by 157 · see citing works
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 141 · see citing works
Self-citationColomar, A., Marty, V., Médina, C., Combe, C., Parnet, P., & Amédée, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304534200 · Cited by 103 · see citing works
A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation.
Sekiyama, A., Ueda, H., Kashiwamura, S., Sekiyama, R., Takeda, M., Rokutan, K., & Okamura, H. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.006 · Cited by 60 · see citing works
Papavlassopoulos, M., Stamme, C., Thon, L., Adam, D., Hillemann, D., Seydel, U., & Schromm, A. B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.4086 · Cited by 50 · see citing works
Scheel, O., Papavlassopoulos, M., Blunck, R., Gebert, A., Härtung, T., Zähringer, U., Seydel, U., & Schromm, A. B. (2006) · Infection and Immunity · doi:10.1128/iai.01783-05 · Cited by 38 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
Self-citationThe NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884 · see citing works
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539 · see citing works
Pyroptosis: host cell death and inflammation
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2070 · Cited by 3,185 · see citing works
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849 · see citing works
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884 · see citing works
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759 · see citing works
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708 · see citing works
Self-citationInnate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658 · see citing works
Self-citationMechanisms and Functions of Inflammasomes
Lamkanfi, M., & Dixit, V. M. (2014) · Cell · doi:10.1016/j.cell.2014.04.007 · Cited by 2,521 · see citing works
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Self-citationOxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis
Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.009 · Cited by 2,282 · see citing works
Inflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230 · see citing works
Muñoz-Planillo, R., Kuffa, P., Martínez-Colón, G. J., Smith, B. L., Rajendiran, T. M., & Núñez, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.016 · Cited by 2,167 · see citing works
Targeting the NLRP3 inflammasome in inflammatory diseases
Mangan, M. S. J., Olhava, E. J., Roush, W. R., Seidel, H. M., Glick, G. D., & Latz, E. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.97 · Cited by 1,885 · see citing works
Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., & Nuñez, G. (2009) · Nature Immunology · doi:10.1038/ni.1703 · Cited by 1,834 · see citing works
NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?
Tschopp, J., & Schroder, K. (2010) · Nature reviews. Immunology · doi:10.1038/nri2725 · Cited by 1,859 · see citing works
Self-citationThe roles of TLRs, RLRs and NLRs in pathogen recognition
Kawai, T., & Akira, S. (2009) · International Immunology · doi:10.1093/intimm/dxp017 · Cited by 1,666 · see citing works
The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases
Davis, B. K., Wen, H., & Ting, J. P.-Y. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101405 · Cited by 1,618 · see citing works
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Eisenbarth, S. C., Colegio, O. R., O’Connor, W., Sutterwala, F. S., & Flavell, R. A. (2008) · Nature · doi:10.1038/nature06939 · Cited by 1,542 · see citing works
Molecular mechanisms regulating NLRP3 inflammasome activation
Jo, E.-K., Kim, J. K., Shin, D.-M., & Sasakawa, C. (2016) · Cellular & Molecular Immunology · doi:10.1038/cmi.2015.95 · Cited by 1,378 · see citing works
NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux
He, Y., Zeng, M. Y., Yang, D., Motro, B., & Núñez, G. (2016) · Nature · doi:10.1038/nature16959 · Cited by 1,295 · see citing works
Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors
Yang, Y., Wang, H., Kouadir, M., Song, H., & Shi, F. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1413-8 · Cited by 1,287 · see citing works
Reactive oxygen species and mitochondria: A nexus of cellular homeostasis
Dunn, J. D., Álvarez, L., Zhang, X., & Soldati, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.005 · Cited by 1,199 · see citing works
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
Lee, G., Subramanian, N., Kim, A. I., Aksentijevich, I. A., Goldbach‐Mansky, R. T., Sacks, D. B., Germain, R. N., Kastner, D. L., & Chae, J. J. (2012) · Nature · doi:10.1038/nature11588 · Cited by 1,077 · see citing works
Regulation of inflammasome activation
Man, S. M., & Kanneganti, T. (2015) · Immunological Reviews · doi:10.1111/imr.12296 · Cited by 1,071 · see citing works
Intracellular NOD-like Receptors in Host Defense and Disease
Kanneganti, T., Lamkanfi, M., & Núñez, G. (2007) · Immunity · doi:10.1016/j.immuni.2007.10.002 · Cited by 1,056 · see citing works
Rajamäki, K., Lappalainen, J., Öörni, K., Välimäki, E., Matikainen, S., Kovanen, P. T., & Eklund, K. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011765 · Cited by 1,039 · see citing works
Innate immunity in the central nervous system
Ransohoff, R. M., & Brown, M. A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58644 · Cited by 1,034 · see citing works
Sensing and reacting to microbes through the inflammasomes
Franchi, L., Muñoz-Planillo, R., & Núñez, G. (2012) · Nature Immunology · doi:10.1038/ni.2231 · Cited by 1,013 · see citing works
The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
Muruve, D. A., Pétrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., & Tschopp, J. (2008) · Nature · doi:10.1038/nature06664 · Cited by 936 · see citing works
Self-citationAntimicrobial activity of mucosal-associated invariant T cells
Bourhis, L. L., Martin, E., Péguillet, I., Guihot, A., Froux, N., Coré, M., Lévy, E., Dusséaux, M., Meyssonnier, V., Prémel, V., et al. (2010) · Nature Immunology · doi:10.1038/ni.1890 · Cited by 914 · see citing works
Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation
Iyer, S. S., He, Q., Janczy, J. R., Elliott, E. I., Zhong, Z., Olivier, A. K., Sadler, J. J., Knepper-Adrian, V., Han, R., Qiao, L., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.001 · Cited by 939 · see citing works
Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?
Abais, J. M., Xia, M., Zhang, Y., Boini, K. M., & Li, P. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5994 · Cited by 936 · see citing works
Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
Groß, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V. L. J., et al. (2009) · Nature · doi:10.1038/nature07965 · Cited by 922 · see citing works
Self-citationColitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome
Bauer, C. A., Duewell, P., Mayer, C., Lehr, H. A., Fitzgerald, K. A., Dauer, M., Tschopp, J., Endres, S., Latz, E., & Schnurr, M. M. (2010) · Gut · doi:10.1136/gut.2009.197822 · Cited by 918 · see citing works
Self-citationThe Nalp3 inflammasome is essential for the development of silicosis
Cassel, S. L., Eisenbarth, S. C., Iyer, S. S., Sadler, J. J., Colegio, O. R., Tephly, L. A., Carter, A. B., Rothman, P. B., Flavell, R. A., & Sutterwala, F. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803933105 · Cited by 907 · see citing works
Function of Nod‐like receptors in microbial recognition and host defense
Franchi, L., Warner, N. E., Viani, K. L., & Núñez, G. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00734.x · Cited by 900 · see citing works
Kawaguchi, M., Takahashi, M., Hata, T., Kashima, Y., Usui, F., Morimoto, H., Izawa, A., Takahashi, Y., Masumoto, J., Koyama, J., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.982777 · Cited by 884 · see citing works
Bulua, A. C., Simon, A., Maddipati, R., Pelletier, M., Park, H., Kim, K.-Y., Sack, M. N., Kastner, D. L., & Siegel, R. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102049 · Cited by 860 · see citing works
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · see citing works
Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity
He, H., Jiang, H., Chen, Y., Ye, J., Wang, A., Wang, C., Liu, Q., Liang, G., Deng, X., Jiang, W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04947-6 · Cited by 827 · see citing works
Initiation and perpetuation of <scp>NLRP</scp> 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821 · see citing works
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., et al. (2014) · Nature Immunology · doi:10.1038/ni.2919 · Cited by 790 · see citing works
Netea, M. G., Nold‐Petry, C. A., Nold, M. F., Joosten, L. A. B., Opitz, B., van der Meer, J. H. M., van de Veerdonk, F. L., Ferwerda, G., Heinhuis, B., Devesa, I., et al. (2008) · Blood · doi:10.1182/blood-2008-03-146720 · Cited by 787 · see citing works
Human Monocytes Engage an Alternative Inflammasome Pathway
Gaidt, M. M., Ebert, T. S., Chauhan, D., Schmidt, T., Schmid-Burgk, J. L., Rapino, F. A., Robertson, A. A. B., Cooper, M. A., Graf, T., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.012 · Cited by 780 · see citing works
The inflammasome: an integrated view
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01046.x · Cited by 778 · see citing works
Self-citationNOD-Like Receptors: Role in Innate Immunity and Inflammatory Disease
Chen, G., Shaw, M. H., Kim, Y., & Núñez, G. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092239 · Cited by 770 · see citing works
Ion Channels in Innate and Adaptive Immunity
Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 764 · see citing works
Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders
Jiang, H., He, H., Chen, Y., Huang, W., Cheng, J., Ye, J., Wang, A., Tao, J., Wang, C., Liu, Q., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171419 · Cited by 771 · see citing works
Autophagy Controls IL-1β Secretion by Targeting Pro-IL-1β for Degradation
Harris, J., Hartman, M., Roche, C., Zeng, S. G., O'Shea, A., Sharp, F. A., Lambe, E. M., Creagh, E. M., Golenbock, D. T., Tschopp, J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202911 · Cited by 794 · see citing works
Self-citationMechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736 · see citing works
Mechanisms of Action of Adjuvants
Awate, S., Babiuk, L. A., & Mutwiri, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00114 · Cited by 741 · see citing works
Abderrazak, A., Syrovets, T., Couchie, D., Hadri, K. E., Friguet, B., Simmet, T., & Rouis, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.008 · Cited by 737 · see citing works
The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation
Sharma, D., & Kanneganti, T. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201602089 · Cited by 733 · see citing works
The inflammasome: a danger sensing complex triggering innate immunity
Pétrilli, V., Dostert, C., Muruve, D. A., & Tschopp, J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.09.002 · Cited by 700 · see citing works
Self-citationPharmacological Inhibitors of the NLRP3 Inflammasome
Zahid, A., Li, B., Kombe, A. J. K., Jin, T., & Tao, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02538 · Cited by 671 · see citing works
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · see citing works
The role of interleukin-1 in general pathology
Kaneko, N., Kurata, M., Yamamoto, T., Morikawa, S., & Masumoto, J. (2019) · Inflammation and Regeneration · doi:10.1186/s41232-019-0101-5 · Cited by 616 · see citing works
Interplay Between NLRP3 Inflammasome and Autophagy
Biasizzo, M., & Kopitar‐Jerala, N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.591803 · Cited by 620 · see citing works
Kool, M., Pétrilli, V., Smedt, T. D., Rolaz, A., Hammad, H., van Nimwegen, M., Bergen, I. M., Castillo, R., Lambrecht, B. N., & Tschopp, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3755 · Cited by 612 · see citing works
Self-citationInflammation in gout: mechanisms and therapeutic targets
So, A. K.-L., & Martinon, F. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.155 · Cited by 619 · see citing works
Self-citationSignaling by ROS drives inflammasome activation
Martinon, F. (2010) · European Journal of Immunology · doi:10.1002/eji.200940168 · Cited by 604 · see citing works
Self-citationLi, N., Zhou, H., Wu, H., Wu, Q., Duan, M., Deng, W., & Tang, Q. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101215 · Cited by 595 · see citing works
Tetherin Inhibits HIV-1 Release by Directly Tethering Virions to Cells
Pérez-Caballero, D., Zang, T. M., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009) · Cell · doi:10.1016/j.cell.2009.08.039 · Cited by 590 · see citing works
Zheng, M., & Kanneganti, T. (2020) · Immunological Reviews · doi:10.1111/imr.12909 · Cited by 591 · see citing works
Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies
Codolo, G., Plotegher, N., Pozzobon, T., Brucale, M., Tessari, I., Bubacco, L., & de Bernard, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055375 · Cited by 585 · see citing works
Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome
Chen, I.-Y., Moriyama, M., Chang, M., & Ichinohe, T. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00050 · Cited by 548 · see citing works
Energy metabolism and inflammation in brain aging and Alzheimer’s disease
Yin, F., Sancheti, H., Patil, I., & Cadenas, E. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.200 · Cited by 538 · see citing works
Caspase‐11 activates a canonical NLRP3 inflammasome by promoting K + efflux
Rühl, S., & Brož, P. (2015) · European Journal of Immunology · doi:10.1002/eji.201545772 · Cited by 546 · see citing works
Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome
Sharp, F. A., Ruane, D., Claass, B., Creagh, E. M., Harris, J., Malyala, P., Singh, M., O’Hagan, D. T., Pétrilli, V., Tschopp, J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804897106 · Cited by 536 · see citing works
Self-citationThe Pannexin 1 Channel Activates the Inflammasome in Neurons and Astrocytes
Silverman, W. R., Vaccari, J. P. D. R., Locovei, S., Qiu, F., Carlsson, S. K., Scemes, E., Keane, R. W., & Dahl, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.004804 · Cited by 534 · see citing works
Yazdi, A. S., Guarda, G., Riteau, N., Drexler, S. K., Tardivel, A., Couillin, I., & Tschopp, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008155107 · Cited by 525 · see citing works
Self-citationPoeck, H., Bscheider, M., Groß, O., Finger, K., Roth, S., Rebsamen, M., Hannesschläger, N., Schlee, M., Rothenfußer, S., Barchet, W., et al. (2009) · Nature Immunology · doi:10.1038/ni.1824 · Cited by 518 · see citing works
Tranilast directly targets NLRP3 to treat inflammasome‐driven diseases
Huang, Y., Jiang, H., Chen, Y., Wang, X., Yang, Y., Tao, J., Deng, X., Liang, G., Zhang, H., Jiang, W., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708689 · Cited by 521 · see citing works
Vance, R. E., Isberg, R. R., & Portnoy, D. A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.06.007 · Cited by 512 · see citing works
Reactive Oxygen Species in the Immune System
Yang, Y., Bazhin, A. V., Werner, J., & Karakhanova, S. (2013) · International Reviews of Immunology · doi:10.3109/08830185.2012.755176 · Cited by 508 · see citing works
Inflammaging: disturbed interplay between autophagy and inflammasomes
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2012) · Aging · doi:10.18632/aging.100444 · Cited by 511 · see citing works
Inflammasomes in liver diseases
Szabó, G., & Csák, T. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.03.035 · Cited by 498 · see citing works
Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner
Conos, S. A., Chen, K. W., De Nardo, D., Hara, H., Whitehead, L., Núñez, G., Masters, S. L., Murphy, J. M., Schroder, K., Vaux, D. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613305114 · Cited by 485 · see citing works
IL-1β Processing in Host Defense: Beyond the Inflammasomes
Netea, M. G., Simon, A., van de Veerdonk, F. L., Kullberg, B. J., van der Meer, J. W. M., & Joosten, L. A. B. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000661 · Cited by 496 · see citing works
Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490 · see citing works
The role of mitochondria in NLRP3 inflammasome activation
Liu, Q., Zhang, D., Hu, D., Zhou, X., & Zhou, Y. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.09.010 · Cited by 475 · see citing works
Fann, D. Y., Lee, S.-Y., Manzanero, S., Tang, S.-C., Gelderblom, M., Chunduri, P., Bernreuther, C., Glatzel, M., Cheng, Y.-L., Thundyil, J., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.326 · Cited by 476 · see citing works
Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors
Bábelová, A., Moreth, K., Tsalastra, W., Zeng-Brouwers, J., Eickelberg, O., Young, M. F., Brückner, P., Pfeilschifter, J. M., Schaefer, R. M., Gröne, H., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014266 · Cited by 474 · see citing works
Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion
Mulay, S. R., Kulkarni, O. P., Rupanagudi, K. V., Migliorini, A., Darisipudi, M. N., Vilaysane, A., Muruve, D. A., Shi, Y., Munro, F., Liapis, H., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63679 · Cited by 474 · see citing works
NLRP3 inflammasome in neurological diseases, from functions to therapies
Song, L., Pei, L., Yao, S., Wu, Y., & Shang, Y. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00063 · Cited by 467 · see citing works
Homeostasis-altering molecular processes as mechanisms of inflammasome activation
Liston, A., & Masters, S. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.151 · Cited by 459 · see citing works
Groß, O., Yazdi, A. S., Thomas, C. J., Masin, M., Heinz, L. X., Guarda, G., Quadroni, M., Drexler, S. K., & Tschopp, J. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.018 · Cited by 460 · see citing works
Self-citationThe inflammasomes: mechanisms of activation and function
Latz, E. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.12.004 · Cited by 455 · see citing works
NLRP3 inflammasome: Its regulation and involvement in atherosclerosis
Hoseini, Z. S., Sepahvand, F., Rashidi, B., Sahebkar, A., Masoudifar, A., & Mirzaei, H. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25930 · Cited by 458 · see citing works
Schmid-Burgk, J. L., Chauhan, D., Schmidt, T., Ebert, T. S., Reinhardt, J., Endl, E., & Hornung, V. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.c115.700492 · Cited by 450 · see citing works
Inflammasome activation and assembly at a glance
Malik, A., & Kanneganti, T. (2017) · Journal of Cell Science · doi:10.1242/jcs.207365 · Cited by 451 · see citing works
Uric acid as a danger signal in gout and its comorbidities
Rock, K. L., Kataoka, H., & Lai, J. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.143 · Cited by 453 · see citing works
The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson's disease
Wang, S., Yuan, Y., Chen, N., & Wang, H. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.12.019 · Cited by 447 · see citing works
Molecular Mechanism of NLRP3 Inflammasome Activation
Jin, C., & Flavell, R. A. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9440-3 · Cited by 440 · see citing works
NLRP3 Inflammasome—A Key Player in Antiviral Responses
Zhao, C., & Zhao, W. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00211 · Cited by 438 · see citing works
NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis
Hirota, S. A., Ng, J., Lueng, A., Khajah, M. A., Parhar, K. K. S., Li, Y., Lam, V. L., Potentier, M. S., Ng, K., Bawa, M., et al. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21478 · Cited by 434 · see citing works
Self-citation
- Authors
- Pétrilli, V, Papin, S., Dostert, C., Mayor, A., Martinon, F., & Tschopp, J.
- Affiliations
- University of Lausanne (CH)
- Harvard University (US)
- Corresponding author
- Tschopp, J
- Venue
- Cell Death & Differentiation
- Published
- 2007-06-29
- Volume
- 14
- Issue
- 9
- Pages
- 1583-1589
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1978274182
- Cited by
- 1,445
- References
- 38
- Citations by year
- 2026: 36 · 2025: 54 · 2024: 62 · 2023: 71 · 2022: 85 · 2021: 78 · 2020: 102 · 2019: 86 · 2018: 73 · 2017: 104 · 2016: 70 · 2015: 79 · 2014: 90 · 2013: 101 · 2012: 93
- FWCI
- 25.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- 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
- 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
- NLRP3 inflammasome, potassium efflux, intracellular potassium concentration, caspase-1 activation, inflammasome assembly, NOD-like receptors, damage-associated molecular patterns, uric acid, IL-1β, IL-18
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Calcium-Binding Proteins, Carrier Proteins, Cell Line, Humans, Inflammation, Mice, Inbred BALB C, Mice, Inbred C57BL, Potassium, Macrophages, Peritoneal, Caspase 1, Interleukin-18, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins, Interleukin-1beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
