Uric acid promotes an acute inflammatory response to sterile cell death in mice
Open accessAbstract
Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death-induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death-induced inflammatory responses in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Reduction of uric acid is associated with substantially reduced neutrophil recruitment in the liver after acetaminophen-induced injury in two different mouse models.
“For example, a reduction of uric acid, which is released from dying cells and has adjuvant activity in vivo21, was associated with substantially reduced neutrophil recruitment in the liver after acetaminophen-induced injury in two different mouse models13.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tolerance, Danger, and the Extended Family
Matzinger, P. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.005015 · Cited by 4,848 · see citing works
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · see citing works
Heart Disease: A Textbook of Cardiovascular Medicine.
(1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-3-415_3 · Cited by 4,119 · see citing works
Apoptosis, oncosis, and necrosis. An overview of cell death.
Majno, G., & Joris, I. (1995) · PubMed · Cited by 3,328 · see citing works
Ames, B. N., Cathcart, R., Schwiers, E., & Hochstein, P. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6858 · Cited by 2,915 · see citing works
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794 · see citing works
How dying cells alert the immune system to danger
Kono, H., & Rock, K. L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2215 · Cited by 1,737 · see citing works
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 · see citing works
Self-citationMolecular identification of a renal urate–anion exchanger that regulates blood urate levels
Enomoto, A., Kimura, H. J., Chairoungdua, A., Shigeta, Y., Jutabha, P., Ho, S., Hosoyamada, M., Takeda, M., Sekine, T., Igarashi, T., et al. (2002) · Nature · doi:10.1038/nature742 · Cited by 1,535 · see citing works
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., et al. (2005) · Nature Medicine · doi:10.1038/nm1315 · Cited by 1,401 · see citing works
Pacher, P., Nivorozhkin, A., & Szabó, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.6 · Cited by 1,218 · see citing works
Maeda, S., Kamata, H., Luo, J., Leffert, H. L., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2005.04.014 · Cited by 1,165 · see citing works
Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog.
Romson, J. L., Hook, B. G., Kunkel, S. L., Abrams, G. D., Schork, M. A., & Lucchesi, B. R. (1983) · Circulation · doi:10.1161/01.cir.67.5.1016 · Cited by 1,164 · see citing works
Mullane, K., Kraemer, R. T., & Smith, B. (1985) · Journal of Pharmacological Methods · doi:10.1016/0160-5402(85)90029-4 · Cited by 974 · see citing works
The Inflammatory Response to Cell Death
Rock, K. L., & Kono, H. (2007) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151456 · Cited by 945 · see citing works
Self-citationChen, C.-J., Kono, H., Golenbock, D., Reed, G., Akira, S., & Rock, K. L. (2007) · Nature Medicine · doi:10.1038/nm1603 · Cited by 876 · see citing works
Self-citationMincle is an ITAM-coupled activating receptor that senses damaged cells
Yamasaki, S., Ishikawa, E., Sakuma, M., Hara, H., Ogata, K., & Saito, T. (2008) · Nature Immunology · doi:10.1038/ni.1651 · Cited by 740 · see citing works
Lotze, M. T., Zeh, H. J., Rubartelli, A., Sparvero, L. J., Amoscato, A. A., Washburn, N. R., DeVera, M., Liang, X., Tör, M., & Billiar, T. R. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00579.x · Cited by 634 · see citing works
Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8
Sekido, N., Mukaida, N., Harada, A., Nakanishi, I., Watanabe, Y., & Matsushima, K. (1993) · Nature · doi:10.1038/365654a0 · Cited by 514 · see citing works
A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation
Weathington, N. M., van Houwelingen, A. H., Noerager, B. D., Jackson, P. L., Kraneveld, A. D., Galin, F. S., Folkerts, G., Nijkamp, F. P., & Blalock, J. E. (2006) · Nature Medicine · doi:10.1038/nm1361 · Cited by 497 · see citing works
IDENTIFICATION OF URATE CRYSTALS IN GOUTY SYNOVIAL FLUID
McCarty, D. J., & Hollander, J. L. (1961) · Annals of Internal Medicine · doi:10.7326/0003-4819-54-3-452 · Cited by 485 · see citing works
Jaeschke, H. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00568.2005 · Cited by 478 · see citing works
Chen, C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28075 · Cited by 475 · see citing works
Self-citationMiyazaki, J., Τακακι, S., Araki, K., Tashiro, F., Tominaga, A., Takatsu, K., & Yamamura, K. (1989) · Gene · doi:10.1016/0378-1119(89)90209-6 · Cited by 446 · see citing works
Mecanismos de lesión hepatocelular
Muntané, J., González, R., Ranchal, I., Collado, J. A., Lopez-Sanchez, L. M., Herencia, C., Rodríguez‐Ariza, A., Muñoz-Castañeda, J. R., & de la Mata, M. (2007) · Revista Española de Enfermedades Digestivas · doi:10.4321/s1130-01082007000700007 · Cited by 349 · see citing works
Neutrophil depletion protects against murine acetaminophen hepatotoxicity†‡
Liu, Z., Han, D., Gunawan, B. K., & Kaplowitz, N. (2006) · Hepatology · doi:10.1002/hep.21175 · Cited by 323 · see citing works
Role of neutrophils in acute inflammatory liver injury
Jaeschke, H., & Hasegawa, T. (2006) · Liver International · doi:10.1111/j.1478-3231.2006.01327.x · Cited by 260 · see citing works
Identification of the target self-antigens in reperfusion injury
Zhang, M., Alicot, E. M., Chiu, I. M., Li, J., Verna, N., Vorup‐Jensen, T., Kessler, B. M., Shimaoka, M., Chan, R. K., Friend, D. S., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20050390 · Cited by 221 · see citing works
Cellular death and necrosis: Chemical, physical and morphologic changes in rat liver
Majno, G., Gattuta, M., & Thompson, T. E. (1960) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00955327 · Cited by 182 · see citing works
Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout
Cammalleri, L., & Malaguarnera, M. (2007) · International Journal of Medical Sciences · doi:10.7150/ijms.4.83 · Cited by 131 · see citing works
Xanthine Oxidoreductase Is an Endogenous Regulator of Cyclooxygenase-2
Ohtsubo, T., Rovira, I. I., Starost, M. F., Liu, C., & Finkel, T. (2004) · Circulation Research · doi:10.1161/01.res.0000149571.96304.36 · Cited by 99 · see citing works
Shi, Y., Galusha, S. A., & Rock, K. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3905 · Cited by 79 · see citing works
Self-citationLeukocyte Depletion Attenuates Reperfusion Injury in Patients With Left Ventricular Hypertrophy
Sawa, Y., Taniguchi, K., Kadoba, K., Nishimura, M., Ichikawa, H., Amemiya, A., Kuratani, T., & Matsuda, H. (1996) · Circulation · doi:10.1161/01.cir.93.9.1640 · Cited by 72 · see citing works
Wilson‐Rawls, J., Deutscher, S. L., & Wold, W. S. M. (1994) · Virology · doi:10.1006/viro.1994.1266 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Decoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022 · see citing works
Pattern Recognition Receptors and the Host Cell Death Molecular Machinery
Amarante-Mendes, G. P., Adjemian, S., Branco, L. M., Zanetti, L. C., Weinlich, R., & Bortoluci, K. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02379 · Cited by 759 · see citing works
The immunology of acute stroke
Chamorro, Á., Meisel, A., Planas, A. M., Urra, X., van de Beek, D., & Veltkamp, R. C. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.98 · Cited by 707 · see citing works
Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions
Yan, M., Huo, Y., Yin, S., & Hu, H. (2018) · Redox Biology · doi:10.1016/j.redox.2018.04.019 · Cited by 687 · see citing works
Sterile inflammation in the liver
Kubes, P., & Mehal, W. Z. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.09.008 · Cited by 666 · see citing works
Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns
Schaefer, L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.619304 · Cited by 618 · see citing works
Inflammasome activation and function in liver disease
Szabó, G., & Petrasek, J. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.94 · Cited by 600 · see citing works
Physiological functions and pathogenic potential of uric acid: A review
Ridi, R. E., & Tallima, H. (2017) · Journal of Advanced Research · doi:10.1016/j.jare.2017.03.003 · Cited by 562 · see citing works
Regulated cell death and inflammation: an auto-amplification loop causes organ failure
Linkermann, A., Stockwell, B. R., Krautwald, S., & Anders, H.-J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3743 · Cited by 522 · see citing works
Immune cells in experimental acute kidney injury
Jang, H. R., & Rabb, H. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.180 · Cited by 522 · see citing works
Damage-associated molecular patterns in cancer: a double-edged sword
Hernandez, C., Huebener, P., & Schwabe, R. F. (2016) · Oncogene · doi:10.1038/onc.2016.104 · Cited by 483 · 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
Self-citationSoluble Uric Acid Activates the NLRP3 Inflammasome
Braga, T. T., Forni, M. F., Corrêa-Costa, M., Ramos, R. N., Barbuto, J. A. M., Branco, P. C., Castoldi, Â., Hiyane, M. I., Davanso, M. R., Latz, E., et al. (2017) · Scientific Reports · doi:10.1038/srep39884 · Cited by 447 · see citing works
Many stimuli pull the necrotic trigger, an overview
Vanlangenakker, N., Berghe, T. V., & Vandenabeele, P. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.164 · Cited by 407 · see citing works
Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity
Tsushima, Y., Nishizawa, H., Tochino, Y., Nakatsuji, H., Sekimoto, R., Nagao, H., Shirakura, T., Kato, K., Imaizumi, K., Takahashi, H., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.485094 · Cited by 393 · see citing works
Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure
Woolbright, B. L., & Jaeschke, H. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.11.017 · Cited by 393 · see citing works
The clearance of dying cells: table for two
Green, D. R., Oguin, T. H., & Martinez, J. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.172 · Cited by 314 · see citing works
The role of neutrophils in immune dysfunction during severe inflammation
Leliefeld, P. H. C., Wessels, C. M., Leenen, L. P. H., Koenderman, L., & Pillay, J. (2016) · Critical Care · doi:10.1186/s13054-016-1250-4 · Cited by 298 · see citing works
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque, R., Sohail, M. A., Malik, A. F., Sarwar, S., Luo, Y., Shah, A., Barrat, F. J., Flavell, R. A., Gorelick, F. S., Husain, S. Z., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.03.041 · Cited by 292 · see citing works
Crișan, T. O., Cleophas, M. C. P., Oosting, M., Lemmers, H., Toenhake-Dijkstra, H., Netea, M. G., Jansen, T., & Joosten, L. A. B. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-206564 · Cited by 289 · see citing works
Sterile inflammation and pregnancy complications: a review
Nadeau‐Vallée, M., Obari, D., Palacios, J. L., Brien, M., Duval, C., Chemtob, S., & Girard, S. (2016) · Reproduction · doi:10.1530/rep-16-0453 · Cited by 274 · see citing works
Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation
Denoble, A. E., Huffman, K. M., Stäbler, T., Kelly, S. J., Hershfield, M. S., McDaniel, G. E., Coleman, R. E., & Kraus, V. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012743108 · Cited by 267 · see citing works
Xanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation
Ives, A., Nomura, J., Martinon, F., Roger, T., LeRoy, D., Miner, J. N., Simon, G., Busso, N., & So, A. (2015) · Nature Communications · doi:10.1038/ncomms7555 · Cited by 264 · see citing works
Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia
Cabău, G., Crișan, T. O., Klück, V., Popp, R. A., & Joosten, L. A. B. (2019) · Immunological Reviews · doi:10.1111/imr.12833 · Cited by 262 · see citing works
Heo, M. J., Kim, T. H., You, J. S., Blaya, D., Sancho‐Bru, P., & Kim, S. G. (2018) · Gut · doi:10.1136/gutjnl-2017-315123 · Cited by 256 · see citing works
Uric acid in health and disease: From physiological functions to pathogenic mechanisms
Wen, S., Arakawa, H., & Tamai, I. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108615 · Cited by 246 · see citing works
Lyngdoh, T., Marques-Vidal, P. M., Paccaud, F. M., Preisig, M., Waeber, G., Bochud, M., & Vollenweider, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019901 · Cited by 242 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Cancer cachexia: impact, mechanisms and emerging treatments
Vaughan, V. C., Martin, P., & Lewandowski, P. A. (2012) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-012-0087-1 · Cited by 233 · see citing works
Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway
Zhou, Y., Fang, L., Jiang, L., Wen, P., Cao, H., He, W., Dai, C., & Yang, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039738 · Cited by 223 · see citing works
Innate and adaptive immune responses to cell death
Rock, K. L., Lai, J., & Kono, H. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01040.x · Cited by 220 · see citing works
Self-citationProcesses of Sterile Inflammation
Shen, H., Kreisel, D., & Goldstein, D. R. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301539 · Cited by 208 · see citing works
Neumann, K., Castiñeiras-Vilariño, M., Höckendorf, U., Hannesschläger, N., Lemeer, S., Kupka, D., Meyermann, S., Lech, M., Anders, H., Küster, B., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.015 · Cited by 202 · see citing works
Savage, C. D., Lopez-Castejon, G., Denes, A., & Brough, D. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00288 · Cited by 197 · see citing works
Uric acid and inflammation in kidney disease
Jung, S. W., Kim, S.-M., Kim, Y., Lee, S. H., & Moon, J.-Y. (2020) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00272.2019 · Cited by 196 · see citing works
Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease
Ponticelli, C. E., Podestà, M. A., & Moroni, G. L. (2020) · Kidney International · doi:10.1016/j.kint.2020.05.056 · Cited by 193 · see citing works
Cellular and molecular mechanisms in liver fibrogenesis
Novo, E., Cannito, S., Paternostro, C., Bocca, C., Miglietta, A., & Parola, M. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.02.015 · Cited by 190 · see citing works
Cancer and Innate Immune System Interactions
Liu, Y., & Zeng, G. (2012) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3182518e83 · Cited by 185 · see citing works
PAMPs and DAMPs as triggers for DIC
Ito, T. (2014) · Journal of Intensive Care · doi:10.1186/s40560-014-0065-0 · Cited by 185 · see citing works
Trauma equals danger—damage control by the immune system
Stoecklein, V. M., Osuka, A., & Lederer, J. A. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0212072 · Cited by 184 · see citing works
Martin, S. J. (2016) · FEBS Journal · doi:10.1111/febs.13775 · Cited by 184 · see citing works
Review of Hyperuricemia as New Marker for Metabolic Syndrome
Billiet, L., Doaty, S., Katz, J. D., & Velasquez, M. T. (2014) · ISRN Rheumatology · doi:10.1155/2014/852954 · Cited by 180 · see citing works
Role of TLRs and DAMPs in allograft inflammation and transplant outcomes
Braza, F., Brouard, S., Chadban, S., & Goldstein, D. R. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.41 · Cited by 177 · see citing works
Trauma alarmins as activators of damage-induced inflammation
Manson, J., Thiemermann, C., & Brohi, K. (2011) · British journal of surgery · doi:10.1002/bjs.7717 · Cited by 174 · see citing works
NLRP3 inflammasome activation in inflammaging
Latz, E., & Duewell, P. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.001 · Cited by 174 · see citing works
Cell Death, Damage-Associated Molecular Patterns, and Sterile Inflammation in Cardiovascular Disease
Zheng, Y., Gardner, S. E., & Clarke, M. C. H. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.224907 · Cited by 168 · see citing works
Uric acid priming in human monocytes is driven by the AKT–PRAS40 autophagy pathway
Crișan, T. O., Cleophas, M. C. P., Novakovic, B., Erler, K., van de Veerdonk, F. L., Stunnenberg, H. G., Netea, M. G., Dinarello, C. A., & Joosten, L. A. B. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620910114 · Cited by 168 · see citing works
Role and mechanisms of autophagy in acetaminophen‐induced liver injury
Chao, X., Wang, H., Jaeschke, H., & Ding, W. (2018) · Liver International · doi:10.1111/liv.13866 · Cited by 163 · see citing works
Uric Acid and Chronic Kidney Disease: Still More to Do
Johnson, R. J., Sánchez‐Lozada, L. G., Lanaspa, M. A., Piani, F., & Borghi, C. (2022) · Kidney International Reports · doi:10.1016/j.ekir.2022.11.016 · Cited by 163 · see citing works
Histones trigger sterile inflammation by activating the NLRP 3 inflammasome
Allam, R., Darisipudi, M. N., Tschopp, J., & Anders, H. (2013) · European Journal of Immunology · doi:10.1002/eji.201243224 · Cited by 159 · see citing works
The sterile immune response during hepatic ischemia/reperfusion
van Golen, R. F., van Gulik, T. M., & Heger, M. (2012) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2012.04.006 · Cited by 158 · see citing works
Kimura, Y., Yanagida, T., Onda, A., Tsukui, D., Hosoyamada, M., & Kono, H. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313224 · Cited by 156 · see citing works
Self-citationCataract Surgery Induces Retinal Pro-inflammatory Gene Expression and Protein Secretion
Xu, H., Chen, M., Forrester, J. V., & Lois, N. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6001 · Cited by 154 · see citing works
The Dynamic Interplay Between Cardiac Inflammation and Fibrosis
Thomas, T. P., & Grisanti, L. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.529075 · Cited by 146 · see citing works
Evans, C. R., Karnovsky, A., Kovach, M. A., Standiford, T. J., Burant, C., & Stringer, K. A. (2013) · Journal of Proteome Research · doi:10.1021/pr4007624 · Cited by 138 · see citing works
Iracheta‐Vellve, A., Petrášek, J., Satishchandran, A., Gyöngyösi, B., Saha, B., Kodys, K., Fitzgerald, K. A., Kurt‐Jones, E. A., & Szabó, G. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.06.013 · Cited by 134 · see citing works
Urate as a Physiological Substrate for Myeloperoxidase
Meotti, F. C., Jameson, G. N. L., Turner, R., Harwood, D. T., Stockwell, S., Rees, M. D., Thomas, S. R., & Kettle, A. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.172460 · Cited by 133 · see citing works
Metabolomics and Its Application to Acute Lung Diseases
Stringer, K. A., McKay, R. T., Karnovsky, A., Quémerais, B., & Lacy, P. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00044 · Cited by 133 · see citing works
Radiation Exposure Induces Inflammasome Pathway Activation in Immune Cells
Stoecklein, V. M., Osuka, A., Ishikawa, S., Lederer, M. R., Wanke-Jellinek, L., & Lederer, J. A. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303051 · Cited by 132 · see citing works
Yang, X., Li, L., Liu, J., Lv, B., & Chen, F. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2015.10.012 · Cited by 129 · see citing works
Jaeschke, H., & Ramachandran, A. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111240 · Cited by 128 · see citing works
Panzarini, E., Inguscio, V., Fimia, G. M., & Dini, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105778 · Cited by 127 · see citing works
Fleshner, M. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.08.012 · Cited by 126 · see citing works
The Role of Efferocytosis in Autoimmune Diseases
Abdolmaleki, F., Farahani, N., Hayat, S. M. G., Pirro, M., Bianconi, V., Barreto, G. E., & Sahebkar, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01645 · Cited by 125 · see citing works
Elevated uric acid correlates with wound severity
Fernandez, M. L., Upton, Z., Edwards, H. E., Finlayson, K. J., & Shooter, G. K. (2011) · International Wound Journal · doi:10.1111/j.1742-481x.2011.00870.x · Cited by 124 · see citing works
Pollara, J., Edwards, R. W., Lin, L., Bendersky, V. A., & Brennan, T. V. (2018) · JCI Insight · doi:10.1172/jci.insight.121622 · Cited by 124 · see citing works
Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration
Chen, X. M., Burdett, T. C., Desjardins, C. A., Logan, R. A., Cipriani, S., Xu, Y., & Schwarzschild, M. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217296110 · Cited by 123 · see citing works
Elevated Uric Acid Increases the Risk for Acute Kidney Injury
Lapsia, V., Johnson, R. J., Dass, B., Shimada, M., Kambhampati, G., Ejaz, N. I., Arif, A. A., & Ejaz, A. A. (2012) · The American Journal of Medicine · doi:10.1016/j.amjmed.2011.06.021 · Cited by 118 · see citing works
Immunogenic Cell Death: Can It Be Exploited in PhotoDynamic Therapy for Cancer?
Panzarini, E., Inguscio, V., & Dini, L. (2012) · BioMed Research International · doi:10.1155/2013/482160 · Cited by 117 · see citing works
NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury
Xiahou, Z., Wang, X., Shen, J., Zhu, X., Feng, X., Hu, R., Guo, D., Li, H., Tian, Y., Liu, Y., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00930-9 · Cited by 115 · see citing works
Innate immune memory: Implications for host responses to damage‐associated molecular patterns
Crișan, T. O., Netea, M. G., & Joosten, L. A. B. (2016) · European Journal of Immunology · doi:10.1002/eji.201545497 · Cited by 112 · see citing works
Greenhalgh, A. D., Brough, D., Robinson, E. M., Girard, S., Rothwell, N. J., & Allan, S. M. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.008557 · Cited by 111 · see citing works
Antitumor Immunity by Magnetic Nanoparticle-Mediated Hyperthermia
Kobayashi, T., Kakimi, K., Nakayama, E., & Jimbow, K. (2014) · Nanomedicine · doi:10.2217/nnm.14.106 · Cited by 106 · see citing works
Danger Signaling in Atherosclerosis
Zimmer, S., Grebe, A., & Latz, E. (2015) · Circulation Research · doi:10.1161/circresaha.116.301135 · Cited by 101 · see citing works
Romi, M. M., Arfian, N., Tranggono, U., Setyaningsih, W. A. W., & Sari, D. C. R. (2017) · BMC Nephrology · doi:10.1186/s12882-017-0736-x · Cited by 100 · see citing works
Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an Alarmin
Ferhat, M., Robin, A., Giraud, S., Sena, S., Goujon, J., Touchard, G., Hauet, T., Girard, J., Gombert, J., Herbelin, A., et al. (2018) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017060650 · Cited by 99 · see citing works
The role of uric acid in inflammasome-mediated kidney injury
Braga, T. T., Foresto‐Neto, O., & Câmara, N. O. S. (2020) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000619 · Cited by 91 · see citing works
Estimation of post-mortem interval using biochemical markers
Donaldson, A. E., & Lamont, I. L. (2013) · Australian Journal of Forensic Sciences · doi:10.1080/00450618.2013.784356 · Cited by 88 · see citing works
Stanzione, R., Forte, M., Cotugno, M., Bianchi, F., Marchitti, S., & Rubattu, S. D. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00966-4 · Cited by 87 · see citing works
Shenashen, M. A., Emran, M. Y., Sabagh, A. E., Selim, M. M., Elmarakbi, A. M., & El‐Safty, S. A. (2021) · Progress in Materials Science · doi:10.1016/j.pmatsci.2021.100866 · Cited by 87 · see citing works
Banu, S., Jabir, N. R., Mohan, R., Manjunath, N. C., Kamal, M. A., Kumar, K. R. V., Zaidi, S. K., Khan, M. S., & Tabrez, S. S. M. (2014) · Journal of Periodontology · doi:10.1902/jop.2014.140414 · Cited by 87 · see citing works
Oncolytic Viruses as Anticancer Vaccines
Woller, N., rlevik, E. G. ⁄., Ureche, C.-I., Schumacher, A., & hnel, F. K. ⁄. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00188 · Cited by 85 · see citing works
Lai, J.-J., Cruz, F. M., & Rock, K. L. (2020) · Immunity · doi:10.1016/j.immuni.2019.11.013 · Cited by 84 · see citing works
Self-citationBrien, M., Duval, C., Palacios, J. L., Boufaied, I., Thibeault, A.-A. H., Nadeau‐Vallée, M., Vaillancourt, C., Sibley, C. P., Abrahams, V. M., Jones, R. L., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1601179 · Cited by 85 · see citing works
Hyaluronan digestion controls DC migration from the skin
Muto, J., Morioka, Y., Yamasaki, K., Kim, M., Garcia, A., Carlin, A. F., Varki, A., & Gallo, R. L. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67947 · Cited by 84 · see citing works
Uric Acid Induces Cognitive Dysfunction through Hippocampal Inflammation in Rodents and Humans
Shao, X., Lu, W., Gao, F., Li, D., Hu, J., Li, Y., Zuo, Z., Jie, H., Zhao, Y., & Cen, X. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1480-16.2016 · Cited by 83 · see citing works
Kato, J., & Svensson, C. I. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2014.11.014 · Cited by 83 · see citing works
Caught red-handed: uric acid is an agent of inflammation
Shi, Y. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43132 · Cited by 82 · see citing works
Milanesi, S., Verzola, D., Cappadona, F., Bonino, B., Murugavel, A., Pontremoli, R., Garibotto, G., & Viazzi, F. C. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27929 · Cited by 78 · see citing works
Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options
Cai, X., Cai, H., Wang, J., Yang, Q., Guan, J., Deng, J., & Chen, Z. (2022) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2100977 · Cited by 78 · see citing works
The impact of sterile inflammation in acute liver injury
Woolbright, B. L. (2017) · Journal of Clinical and Translational Research · doi:10.18053/jctres.03.2017s1.003 · Cited by 78 · see citing works
Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair
Peiseler, M., & Kubes, P. (2018) · European Journal of Trauma and Emergency Surgery · doi:10.1007/s00068-018-0956-1 · Cited by 77 · see citing works
Novel developments in the prophylaxis and treatment of acute GVHD
JAMY, O. H., Zeiser, R., & Chen, Y. (2023) · Blood · doi:10.1182/blood.2023020073 · Cited by 75 · see citing works
Molecular determinants of sterile inflammation
Kono, H., Onda, A., & Yanagida, T. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.12.004 · Cited by 75 · see citing works
Self-citationThe Inflammasome in Liver Injury and Non-Alcoholic Fatty Liver Disease
Mehal, W. Z. (2014) · Digestive Diseases · doi:10.1159/000360495 · Cited by 74 · see citing works
Neogi, T., Casella, G., Rekhraj, S., Struthers, A. D., Choi, H. K., & Terkeltaub, R. A. (2011) · Arthritis & Rheumatism · doi:10.1002/art.33369 · Cited by 73 · see citing works
Lech, M., Gröbmayr, R., Weidenbusch, M. J., & Anders, H. (2012) · Mediators of Inflammation · doi:10.1155/2012/951390 · Cited by 73 · see citing works
Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development
Ignat, S.-R., Dinescu, S., Hermenean, A. O., & Costache, M. (2020) · Cells · doi:10.3390/cells9020461 · Cited by 72 · see citing works
Lichtnekert, J., Kulkarni, O. P., Mulay, S. R., Rupanagudi, K. V., Ryu, M., Allam, R., Vielhauer, V., Muruve, D. A., Lindenmeyer, M. T., Cohen, C. D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026778 · Cited by 71 · see citing works
- Authors
- Kono, H., Chen, C.-J., Ontiveros, F., & Rock, K. L.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- National Taiwan University (TW)
- Corresponding author
- Rock, Kenneth L.
- Venue
- Journal of Clinical Investigation
- Published
- 2010-06-01
- Volume
- 120
- Issue
- 6
- Pages
- 1939-1949
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2877935
- OpenAlex
- W2092946161
- Cited by
- 337
- References
- 34
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 16 · 2023: 13 · 2022: 19 · 2021: 18 · 2020: 24 · 2019: 17 · 2018: 27 · 2017: 24 · 2016: 33 · 2015: 22 · 2014: 26 · 2013: 22 · 2012: 29
- FWCI
- 18.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Sanofi
- American Asthma Foundation
- National Institutes of Health (DK32520)
- National Institute of Allergy and Infectious Diseases (R01AI043543, R01AI078287)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 32520, P30DK032520)
- Topics
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- uric acid, sterile inflammation, necrosis, cell death, inflammation, nucleic acid degradation, proinflammatory molecules, innate immunity
- MeSH terms
- Animals, Cells, Immune System, Inflammation, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Necrosis, Uric Acid, Cell Death, Mice
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
