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Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes
Open accessAbstract
Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro. Processing of IL-1β initiated by IAPP first required priming, a process that involved glucose metabolism and was facilitated by minimally oxidized low-density lipoprotein. Finally, mice transgenic for human IAPP had more IL-1β in pancreatic islets, which localized together with amyloid and macrophages. Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP.
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In the citing paper
“that induce interleukin (IL)-1β release to recruit macrophages and enhance local islet inflammation ( 45 ).”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [45]
Experimental — accuracy not yet measuredIn the citing paper
“A potential role for NLRP3 in promoting elevated levels of IL-1β in type 2 diabetes was also implied by the observation of NLRP3-dependent IL-1β secretion by mouse bone marrow-derived macrophages and dendritic cells in response to islet amyloid polypeptide (IAPP), which is deposited in the pancreas and associated with loss of β-cell function in type 2 diabetes61.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
In the citing paper
“Interestingly, the anti-diabetic drug glyburide (Glibenclamide; Roche/Sanofi-Aventis) has been shown to block glucose-mediated secretion of IL-1β by mouse pancreatic islets62, as well as IL-1β production by macrophages in response to IAPP61, and NLRP3-deficient mice were more glucose tolerant than wild-type mice62.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
In the citing paper
“In a separate study, no differences in IL-1β secretion were observed between wild-type and TXNIP-deficient bone marrow-derived macrophages in response to several NLRP3 stimuli, including MSU crystals and ATP61.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
In the citing paper
“However, the role of TXNIP and ROS in NLRP3 activation has been challenged.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
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Cites
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
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
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Self-citationTLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,087
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
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
Innate 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
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Interleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798
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The 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
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176
Self-citationType 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737
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
“However, a different study found that TXNIP is dispensable for NLRP3 inflammasome activation that is induced by ATP, MSU, and islet amyloid polypeptide [159].”
BackgroundInflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
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
Self-citationMechanisms and Functions of Inflammasomes
Lamkanfi, M., & Dixit, V. M. (2014) · Cell · doi:10.1016/j.cell.2014.04.007 · Cited by 2,579
“, 2013) have important roles in the Nlrp3 pathway (Ermler et al., 2014; He et al., 2013; Masters et al., 2010; Muñoz-Planillo et al., 2013).”
BackgroundInfluentialInflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435
Oxidized 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
“NLRP3 has been shown to play an important role in type II diabetes (Masters et al., 2010) and interestingly, high concentrations of 8-OH-dG (representative of damaged DNA) have been associated with both type I and type II diabetes (Hinokio et al., 1999; Simone et al., 2008).”
BackgroundInflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes
Esser, N., Legrand-Poels, S., Piette, J., Scheen, A. J., & Paquot, N. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.04.006 · Cited by 1,981
“Moreover, islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas, seems to contribute to IL-1b production in islets through activation of the NLRP3 inflammasome [54].”
BackgroundInterleukin-1 in the pathogenesis and treatment of inflammatory diseases
Dinarello, C. A. (2011) · Blood · doi:10.1182/blood-2010-07-273417 · Cited by 2,248
Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling
Wen, H., Gris, D., Lei, Y., Jha, S., Zhang, L., Huang, M. T.-H., Brickey, W. J., & Ting, J. P.-Y. (2011) · Nature Immunology · doi:10.1038/ni.2022 · Cited by 1,698
Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases
Dinarello, C. A., Simon, A., & van der Meer, J. W. M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3800 · Cited by 1,812
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
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
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314
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 1,233
NLRP3 inflammasome in cancer and metabolic diseases
Sharma, B. R., & Kanneganti, T. (2021) · Nature Immunology · doi:10.1038/s41590-021-00886-5 · Cited by 1,129
Regulation of inflammasome activation
Man, S. M., & Kanneganti, T. (2015) · Immunological Reviews · doi:10.1111/imr.12296 · Cited by 1,088
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044
“An interesting recent finding is that aggregated IAPP can activate the inflammasome to produce processed interleukin-1 , which may cause -cell death (237).”
BackgroundThe vagus nerve and the inflammatory reflex – linking immunity and metabolism
Pavlov, V. A., & Tracey, K. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.189 · Cited by 1,040
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 1,046
Self-citationNLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis
Grebe, A., Hoss, F., & Latz, E. (2018) · Circulation Research · doi:10.1161/circresaha.118.311362 · Cited by 926
“It was shown that the pancreatic islet amyloid polypeptide, which is co-secreted with insulin, forms aggregates, which induce NLRP3dependent IL-1β secretion as well as NLRP3-dependent cell death of insulin-producing β-cells.(135,136) Moreover, saturated fatty acids were also shown to activate NLRP3 and thus promote ty…”
BackgroundSheedy, F. J., Grebe, A., Rayner, K. J., Kalantari, P., Ramkhelawon, B., Carpenter, S. B., Becker, C. E., Ediriweera, H. N., Mullick, A. E., Golenbock, D. T., et al. (2013) · Nature Immunology · doi:10.1038/ni.2639 · Cited by 935
“In the AD brain and diabetic pancreas, amyloid plaques arise from the aggregation of pre-fibrillar amyloidogenic peptides such as the Aβ(1-42) peptide17, 18, 19 or IAPP20, 21, 22, which oligomerize and give rise to higher order structures, including fibrils.”
BackgroundSelf-citationRedox 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
Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome
Misawa, T., Takahama, M., Kozaki, T., Lee, H., Zou, J., Saitoh, T., & Akira, S. (2013) · Nature Immunology · doi:10.1038/ni.2550 · Cited by 894
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
Initiation and perpetuation of NLRP 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821
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
Yan, Y., Jiang, W., Spinetti, T., Tardivel, A., Castillo, R., Bourquin, C., Guarda, G., Tian, Z., Tschopp, J., & Zhou, R. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.015 · Cited by 784
“As we and others have shown that the NLRP3 inflammasome is implicated in the development of insulin resistance in T2D (Masters et al., 2010; Vandanmagsar et al., 2011; Wen et al., 2011; Zhou et al., 2010), we investigated whetheru-3 FAs can improve insulin sensitivity via inhibition of inflammasome activation.”
BackgroundInfluentialThe 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
“However, other reports were unable to reproduce some of these findings (115), so it remains to be determined in what cell types and under what circumstances TXNIP contributes to inflammasome activation.”
ResultA clinical perspective of IL‐1β as the gatekeeper of inflammation
Dinarello, C. A. (2011) · European Journal of Immunology · doi:10.1002/eji.201141550 · Cited by 792
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 783
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
Self-citationThe adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
Franklin, B. S., Bossaller, L., De Nardo, D., Ratter, J. M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S. R., Al-Amoudi, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2913 · Cited by 773
The role of oxidative stress during inflammatory processes
Lugrin, J., Rosenblatt‐Velin, N., Parapanov, R., & Liaudet, L. (2013) · Biological Chemistry · doi:10.1515/hsz-2013-0241 · Cited by 766
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 749
“…. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304”
BackgroundRole of pyroptosis in inflammation and cancer
Xiang, W. D., Xie, F., Zhou, X., Wu, Y., Yan, H., Liu, T., Huang, J. S., Wang, F., Zhou, F., & Zhang, L. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00905-x · Cited by 728
Regulation of metabolism by the innate immune system
Lackey, D. E., & Olefsky, J. M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.189 · Cited by 667
Targeting inflammation in the treatment of type 2 diabetes: time to start
Donath, M. Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4275 · Cited by 690
Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging
Youm, Y.-H., Grant, R. W., McCabe, L. R., Albarado, D. C., Nguyen, K. Y., Ravussin, A., Pistell, P., Newman, S., Carter, R., Laque, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.010 · Cited by 674
“…and excessive Nlrp3 inflammasome activation has been implicated in chronic diseases such as Alzheimer’s diseases (Heneka et al., 2013), diabetes (Masters et al., 2010; Vandanmagsar et al., 2011; Wen et al., 2011; Youm et al., 2011), athero- Cell sclerosis (Duewell et al., 2010), arthritis, and…”
Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes
Scheithauer, T. P. M., Rampanelli, E., Nieuwdorp, M., Vallance, B. A., Verchere, C. B., van Raalte, D. H., & Herrema, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571731 · Cited by 715
Pharmacological 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
“NLRP3 Inflammasome can also respond to damage-associated endogenous factors such as drusen (15), uric acid crystals (16), extracellular adenosine triphosphate (ATP) (17), β-amyloid plaques (11), and islet amyloid polypeptide (18).”
BackgroundWalsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637
The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation
Hooftman, A., Angiari, S., Hester, S., Corcoran, S. E., Runtsch, M. C., Ling, C., Ruzek, M. C., Slivka, P. F., McGettrick, A. F., Banahan, K., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.07.016 · Cited by 632
Self-citationThe 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 650
“Indeed, islet amyloid polypeptide (IAPP) oligomers activated NLRP3 inflammasomes to induce significant IL-1β production by infiltrating macrophages in an in vivo study [105, 106] .”
BackgroundThe inflammation highway: metabolism accelerates inflammatory traffic in obesity
Johnson, A. R., Justin Milner, J., & Makowski, L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01151.x · Cited by 603
“Finally, glucose metabolism has also been demonstrated to be essential to NLRP3-mediated inflammasome activation (250, 251).”
BackgroundDICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592
“Subsequently, endogenous crystals, polypeptides, and lipids were reported to activate it in diseases such as gout, atherogenesis, Alzheimer’s disease, and type 2 diabetes (Halle et al., 2008; Masters et al., 2010; Muruve et al., 2008; Wen et al., 2011).”
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
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
Autophagy balances inflammation in innate immunity
Deretic, V., & Levine, B. (2018) · Autophagy · doi:10.1080/15548627.2017.1402992 · Cited by 563
Targeting immunometabolism as an anti-inflammatory strategy
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2020) · Cell Research · doi:10.1038/s41422-020-0291-z · Cited by 590
Self-citationMicroglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556
“In addition of Aβ, cholesterol crystals is also amajor causative factor of age-related diseases such as atherosclerosis, and also shows activation of the inflammasome in a CatB-dependent manner (Duewell et al., 2010; Masters et al., 2010).”
BackgroundMechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors
Zelniker, T. A., & Braunwald, E. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.031 · Cited by 596
Interleukin-18 in Health and Disease
Yasuda, K., Nakanishi, K., & Tsutsui, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030649 · Cited by 583
“However, soon after their discovery, PRRs were demonstrated to sense various self-derived molecules, such as monosodium urate crystals involved in gout [44], calcium pyrophosphate dehydrate crystals involved in pseudogout [44], amyloid b in Alzheimer’s disease [205], and islet amyloid polypeptide in type 2 diabetes me…”
BackgroundTreating inflammation by blocking interleukin-1 in humans
Dinarello, C. A., & van der Meer, J. W. M. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.008 · Cited by 560
NLRP3 inflammasome activity is negatively controlled by miR-223
Bauernfeind, F., Rieger, A., Schildberg, F. A., Knolle, P. A., Schmid-Burgk, J. L., & Hornung, V. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201516 · Cited by 544
“of NLRP3 in many lifestyle-related diseases, such as gout (26), atherosclerosis (27), type 2 diabetes (28), and Alzheimer’s disease (29), pharmacological targeting of this regulatory circuit might constitute a reasonable therapeutic venture.”
BackgroundTranilast 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 531
“…and contribute to the development of human complex diseases, including gout, atherosclerosis, neurodegenerative diseases, and type 2 diabetes (T2D) (Martinon et al , 2006; Duewell et al , 2010; Masters et al , 2010; Zhou et al , 2010; Wen et al , 2011; Heneka et al , 2012; Lamkanfi & Dixit, 2012).”
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 523
“However, these results have not yet been reproduced by other groups [40].”
ResultType 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition
Hameed, I., Masoodi, S. R., Mir, S. A., Nabi, M., Ghazanfar, K., & Ganai, B. A. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i4.598 · Cited by 535
Mechanisms of inflammasome activation: recent advances and novel insights
Vanaja, S. K., Rathinam, V. A. K., & Fitzgerald, K. A. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.12.009 · Cited by 499
Redox regulation of immunometabolism
Muri, J., & Köpf, M. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00478-8 · Cited by 519
Rossol, M., Pierer, M., Raulien, N., Quandt, D., Meusch, U., Rothe, K., Schubert, K. A., Schöneberg, T., Schaefer, M., Krügel, U., et al. (2012) · Nature Communications · doi:10.1038/ncomms2339 · Cited by 506
Immunological complications of obesity
Kanneganti, T., & Dixit, V. D. (2012) · Nature Immunology · doi:10.1038/ni.2343 · Cited by 500
Reactive oxygen species at the crossroads of inflammasome and inflammation
Harijith, A. K., Ebenezer, D. L., & Natarajan, V. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00352 · Cited by 474
Adipocyte dysfunction, inflammation and metabolic syndrome
Klöting, N., & Blüher, M. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9301-0 · Cited by 487
“The important role of interleukin (IL)-1β in the pathogenesis of type 2 diabetes is further supported by clinical trial data demonstrating that an IL-1 blockade by the interleukin-1receptor antagonist anakinra improves glycemia, insulin secretion and reduced markers of systemic inflammation [6].”
BackgroundInfluentialA 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases
Barnett, K. C., Li, S., Liang, K., & Ting, J. P.-Y. (2023) · Cell · doi:10.1016/j.cell.2023.04.025 · Cited by 458
β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
Halban, P. A., Polonsky, K. S., Bowden, D. W., Hawkins, M. A., Ling, C., Mather, K. J., Powers, A. C., Rhodes, C. J., Sussel, L., & Weir, G. C. (2014) · Diabetes Care · doi:10.2337/dc14-0396 · Cited by 460
“levels that allow proapoptotic IAPP oligomers to form (44) that induce interleukin (IL)-1b release to recruit macrophages and enhance local islet inflammation (45).”
BackgroundStancu, I.-C., Cremers, N., Vanrusselt, H., Couturier, J., Vanoosthuyse, A., Kessels, S., Lodder, C., Brône, B., Huaux, F., Octave, J.-N., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-01957-y · Cited by 447
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
“…which leads to the processing and release of IL-1β and IL-18 and eventually potentiates inflammatory responses that are involved in multiple infectious, inflammatory and immune diseases (Sutterwala et al., 2006; Willingham et al., 2007; Halle et al., 2008; Masters et al., 2010; Walsh et al., 2014).”
BackgroundA role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation?
Wen, H., Ting, J. P. ‐., & O'Neill, L. A. J. (2012) · Nature Immunology · doi:10.1038/ni.2228 · Cited by 464
Self-citationUric 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 463
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 452
Daniels, M. J. D., Rivers‐Auty, J., Schilling, T., Spencer, N. G., Watremez, W., Fasolino, V., Booth, S., White, C., Baldwin, A. G., Freeman, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12504 · Cited by 453
Interleukin-1 Beta—A Friend or Foe in Malignancies?
Bent, R., Moll, L., Grabbe, S., & Bros, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082155 · Cited by 475
“Furthermore, minimally oxidized low density lipoproteins were found to be elevated in diabetic patients which triggered IL-1β gene expression via TLR4 engagement [169].”
BackgroundRole of innate and adaptive immunity in obesity-associated metabolic disease
McLaughlin, T., Ackerman, S. E., Shen, L., & Engleman, E. G. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88876 · Cited by 462
“NLRP3 activation, with associated IL-1β and IL-18 secretion, has been observed in response to stimulation by lipotoxicity-related increases in intracellular ceramide (58), palmitate (59), islet amyloid polypeptide (60), serum amyloid A (61), cholesterol crystals (62), and oxidized LDL cholesterol (63).”
BackgroundInnate immunity in diabetes and diabetic nephropathy
Wada, J., & Makino, H. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.175 · Cited by 441
NLRP3 inflammasomes link inflammation and metabolic disease
De Nardo, D., & Latz, E. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.05.004 · Cited by 425
The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases
Toldo, S. A., & Abbate, A. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00946-3 · Cited by 461
“Thioredoxin-interacting protein (TXNIP) links oxidative stress to NLRP3 inflammasome activation 50–52 (Fig.”
InfluentialDoyle, S., Campbell, M., Ozaki, E., Salomon, R. G., Mori, A., Kenna, P. F., Farrar, G. J., Kiang, A., Humphries, M. M., Lavelle, E. C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2717 · Cited by 428
Self-citationRecognition of Bacteria by Inflammasomes
von Moltke, J., Ayres, J. S., Kofoed, E. M., Chavarría‐Smith, J., & Vance, R. E. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095944 · Cited by 420
Targeting innate immune mediators in type 1 and type 2 diabetes
Donath, M. Y., Dinarello, C. A., & Mandrup-Poulsen, T. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0213-9 · Cited by 416
Mechanisms of NOD-like Receptor-Associated Inflammasome Activation
Wen, H., Miao, E. A., & Ting, J. P. ‐. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.037 · Cited by 415
“These studies may reconcile the long-term debate about whether TXNIP plays a role in NLRP3 activation (Masters et al., 2010; Zhou et al., 2010).”
NLRP3 Gene Silencing Ameliorates Diabetic Cardiomyopathy in a Type 2 Diabetes Rat Model
Luo, B., Li, B., Wang, W., Liu, X., Xia, Y., Zhang, C., Zhang, M., Zhang, Y., & An, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104771 · Cited by 408
“One research of type 2 diabetes has shown that the maturation of caspase-1 and IL-1b, the sign of NLRP3 inflammation activation, did not required TXNIP in bone marrow-derived macrophages [48].”
BackgroundDror, E., Dalmas, É., Meier, D. T., Wueest, S., Thévenet, J., Thienel, C., Timper, K., Nordmann, T. M., Traub, S., Schulze, F., et al. (2017) · Nature Immunology · doi:10.1038/ni.3659 · Cited by 411
The NLRP3 inflammasome in health and disease: the good, the bad and the ugly
Menu, P., & Vince, J. E. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04440.x · Cited by 396
Jourdan, T., Godlewski, G., Cinar, R., Bertola, A., Szanda, G., Liu, J., Tam, J., Han, T., Mukhopadhyay, B., Skarulis, M. C., et al. (2013) · Nature Medicine · doi:10.1038/nm.3265 · Cited by 388
Keane, K. N., Cruzat, V. F., Carlessi, R., de Bittencourt, P. I. H., & Newsholme, P. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/181643 · Cited by 401
Self-citationTargeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives
Doyle, S., Ozaki, E., & Campbell, M. (2015) · Journal of Inflammation Research · doi:10.2147/jir.s51250 · Cited by 389
InflammasomesPreprint
de Zoete, M. R., Palm, N. W., Zhu, S., & Flavell, R. A. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016287 · Cited by 399
“Where tested, the effects of NLRP3 deficiency on diabetes in mice are partially phenocopied by IL-1R deficiency (Masters et al. 2010).”
BackgroundRedox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377
“However, this pathway was questioned by experiments in TXNIP-deficient macrophages (185).”
MethodTIM-3 restrains anti-tumour immunity by regulating inflammasome activation
Dixon, K. O., Tabaka, M., Schramm, M. A., Xiao, S., Tang, R., Dionne, D. A., Anderson, A. C., Rozenblatt–Rosen, O., Regev, A., & Kuchroo, V. K. (2021) · Nature · doi:10.1038/s41586-021-03626-9 · Cited by 381
RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation
Moon, J.-S., Hisata, S., Park, M. A., DeNicola, G. M., Ryter, S. W., Nakahira, K., & Choi, A. M. K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.046 · Cited by 379
“The inhibition of glycolysis in macrophages suppressed IL-1b gene expression in response to lipopolysaccharide (LPS) treatment (Masters et al., 2010; Tannahill et al., 2013).”
BackgroundRetractedCircadian rhythms and the gut microbiota: from the metabolic syndrome to cancer
Bishehsari, F., Voigt, R. M., & Keshavarzian, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00427-4 · Cited by 384
Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos
Robinson, N., Ganesan, R., Hegedűs, C., Kovács, K. É., Kufer, T. A., & Virág, L. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101239 · Cited by 375
NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes
Gustin, A., Kirchmeyer, M., Koncina, E., Felten, P., Losciuto, S., Heurtaux, T., Tardivel, A., Heuschling, P., & Dostert, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130624 · Cited by 369
“Besides, the capacity of similar aggregates, such as islet amyloid polypeptide (IAPP) in type II diabetes, to activate NLRP3 inflammasome via abnormal phagocytosis and lysosomal rupture mechanism has also been shown [22].”
Background
Metadata
- Authors
- Masters, S. L., Dunne, A., Subramanian, S. L., Hull, R. L., Tannahill, G. M., Sharp, F. A., Becker, C., Franchi, L., Yoshihara, E., Chen, Z., Mullooly, N., Mielke, L. A., Harris, J., Coll, R. C., Mills, K. H. G., Mok, K. H., Newsholme, P., Nuñez, G., Yodoi, J., Kahn, S. E., Lavelle, E. C., & O'Neill, L. A. J.
- Affiliations
- Trinity College Dublin (IE)
- University of Washington (US)
- University of Michigan (US)
- Kyoto University (JP)
- University College Dublin (IE)
- Corresponding author
- Masters, Seth L
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-09-12
- Volume
- 11
- Issue
- 10
- Pages
- 897-904
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3103663
- OpenAlex
- W2034946303
- Cited by
- 1,330
- References
- 55
- Citations by year
- 2026: 58 · 2025: 57 · 2024: 64 · 2023: 75 · 2022: 71 · 2021: 99 · 2020: 100 · 2019: 95 · 2018: 82 · 2017: 83 · 2016: 73 · 2015: 101 · 2014: 95 · 2013: 112 · 2012: 83
- FWCI
- 35.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- eSpace (Curtin University) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI063331, R56AI063331, R01AI063331, R37AI063331)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-75998, R01DK075998)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- NLRP3 inflammasome, amylin, IL-1β, type 2 diabetes, beta cell destruction, glibenclamide, LDL oxidation, glucose metabolism, inflammasome priming, pancreatic islets, macrophages, amyloid deposition
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Amyloid, Animals, Carrier Proteins, Cells, Cultured, Dendritic Cells, Diabetes Mellitus, Type 2, Glyburide, Humans, Hypoglycemic Agents, Islets of Langerhans, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Cytoplasmic and Nuclear, Mice, Rats, Interleukin-1beta, Islet Amyloid Polypeptide
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