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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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“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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Sorted by citations
Items 301–400 of 1,001
Inflammasomes and Metabolic Disorders: Old Genes in Modern Diseases
Robbins, G. R., Wen, H., & Ting, J. P. ‐. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.029 · Cited by 118
“P A A uthor M anuscript IL-1β release (Masters et al., 2010).”
InfluentialTherapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases
Seok, J. K., Kang, H. C., Cho, Y., Lee, H. S., & Lee, J. Y. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-021-01307-9 · Cited by 122
NLRP inflammasomes in health and disease
Xu, Z., Kombe, A. J. K., Deng, S., Zhang, H., Wu, S., Ruan, J., Zhou, Y. Y., & Jin, T. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00179-x · Cited by 131
Schneider, K. M., Bieghs, V., Heymann, F., Hu, W., Yildiz, D., Liao, L., Frissen, M., Ludwig, A., Gaßler, N., Pabst, O., et al. (2015) · Hepatology · doi:10.1002/hep.27982 · Cited by 112
Wang, X., Zhai, Y., Xu, L., Qiao, C., Sun, X., Ding, J., Lu, M., & Hu, G. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.11.001 · Cited by 112
Yang, S.-M., Ka, S., Wu, H., Yeh, Y.-C., Kuo, C., Hua, K., Shi, G.-Y., Hung, Y.-J., Hsiao, F., Yang, S.-S., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-3115-6 · Cited by 112
Redox control of NLRP3 inflammasome activation in health and disease
Rubartelli, A. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0512265 · Cited by 114
“[41] reported no difference in caspase-1 activation and IL-1 secretion in response to inflammasome activators (including islet amyloid polipeptide) between WT and TXNIP-deficient macrophages, thereby ruling out a role for TXNIP in regulating IL-1 production by the inflammasome.”
BackgroundDysregulation of Natural Killer Cells in Obesity
O'Shea, D. B., & Hogan, A. E. (2019) · Cancers · doi:10.3390/cancers11040573 · Cited by 115
“Several cytokines which are elevated in obese individuals have been shown to disrupt normal homeostatic processes, such as interleukin 1 (IL-1) and insulin signalling, or IL-17 and adipogenesis [18,19].”
BackgroundAn Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology
Ratsimandresy, R. A., Dorfleutner, A., & Stehlik, C. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00440 · Cited by 114
“In response to IAPP, inflammasome priming, which causes the transcriptional upregulation of IL-1β, requires a sufficient glucose metabolism and can be facilitated by minimally oxidized low-density lipoprotein (88).”
BackgroundStressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation
Yabal, M., Calleja, D. J., Simpson, D. S., & Lawlor, K. E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0318-124r · Cited by 110
Li, J.-Y., Wang, Y.-Y., Shao, T., Fan, D., Lin, A., Xiang, L., & Shao, J.-Z. (2020) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)49920-0 · Cited by 110
Liu, S., Bi, Y., Han, T., Li, Y. E., Wang, Q., Wu, N. N., Xu, C., Ge, J., Hu, R., & Zhang, Y. (2024) · Cell Discovery · doi:10.1038/s41421-023-00622-3 · Cited by 112
Apigenin ameliorates HFD-induced NAFLD through regulation of the XO/NLRP3 pathways
Lv, Y., Gao, X., Luo, Y., Fan, W., Shen, T., Ding, C., Yao, M., Song, S., & Yan, L. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.05.015 · Cited by 108
The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation
Shi, F., Yang, L., Kouadir, M., Yang, Y., Wang, J., Zhou, X., Yin, X., & Zhao, D. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-73 · Cited by 112
“Activation of the NLRP3 inflammasome by islet amyloid polypeptide has been also reported in type 2 diabetes [36,37].”
BackgroundDai, Y., Dai, D., Wang, X., Ding, Z., & Mehta, J. L. (2014) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-014-6539-4 · Cited by 116
“OxLDL binds to the scavenger receptors on membrane of macrophages, and stimulates a number of proinflammatory cytokines such as IL-1β that play a role in the progression of atherosclerosis [3,4].”
BackgroundTargeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity
Meier, D. T., Souza, J. D. P., & Donath, M. Y. (2024) · Diabetologia · doi:10.1007/s00125-024-06306-1 · Cited by 124
Enhanced Inflammasome Activity in Patients with Psoriasis Promotes Systemic Inflammation
Verma, D., Fekri, S. Z., Sigurdardottir, G., Bivik, C. A., Sandin, C., & Enerbäck, C. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.07.012 · Cited by 109
“Among the NLRs, NLRP3 is the most extensively studied, and it has been implicated in several chronic inflammatory disorders (Liu et al., 2017; Martinon et al., 2006; Masters et al., 2010; Mathews et al., 2014).”
BackgroundMason, D. R., Beck, P. L., & Muruve, D. A. (2011) · Journal of Innate Immunity · doi:10.1159/000334247 · Cited by 106
Sharma, M., Boytard, L., Hadi, T., Koelwyn, G. J., Simon, R., Ouimet, M. I., Seifert, L., Spiro, W., Yan, B., Hutchison, S. B., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-62272-9 · Cited by 105
Nutritional regulation of insulin secretion: implications for diabetes.
Newsholme, P., & Krause, M. D. S. (2012) · Europe PMC (PubMed Central) · Cited by 108
Self-citationLiu, L., & Chan, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.016 · Cited by 108
“NLRP1 has been shown to be expressed in neurons, and NLRP3 and IPAF have been detected in microglial cells (Jamilloux et al., 2013; Masters et al., 2010).”
InfluentialConforti‐Andreoni, C., Ricciardi‐Castagnoli, P., & Mortellaro, A. (2011) · Cellular and Molecular Immunology · doi:10.1038/cmi.2010.81 · Cited by 109
Metabolic Inflammation-Differential Modulation by Dietary Constituents
Lyons, C. L., Kennedy, E. B., & Roche, H. M. (2016) · Nutrients · doi:10.3390/nu8050247 · Cited by 106
“Human amyloidogenic IAPP activates the Nlrp3 inflammasome to release pro-inflammatory IL-1β from immune cells present in the pancreatic islets [88].”
BackgroundMolecular Mechanisms of Intervertebral Disc Degeneration
Rider, S. M., Mizuno, S., & Kang, J. D. (2018) · Spine Surgery and Related Research · doi:10.22603/ssrr.2017-0095 · Cited by 105
Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model
Erlich, Z., Shlomovitz, I., Edry‐Botzer, L., Cohen, H., Frank, D. O., Wang, H., Lew, A. M., Lawlor, K. E., Zhan, Y., Vince, J. E., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0313-5 · Cited by 100
β-cell autophagy: Mechanism and role in β-cell dysfunction
Lee, Y., Kim, J., Park, K., & Lee, M. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.014 · Cited by 106
The role of lysosome in regulated necrosis
Alu, A., Han, X., Ma, X., Wu, M., Wei, Y., & Wei, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.003 · Cited by 109
Stadler, K. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-5441-0_21 · Cited by 106
Lopalco, G., Cantarini, L., Vitale, A., Iannone, F., Anelli, M. G., Andreozzi, L., Lapadula, G., Galeazzi, M., & Rigante, D. (2015) · Mediators of Inflammation · doi:10.1155/2015/194864 · Cited by 105
Lipids, inflammasomes, metabolism, and disease
Anand, P. (2020) · Immunological Reviews · doi:10.1111/imr.12891 · Cited by 108
The Inflammasome in Times of COVID-19
Vaccari, J. C. D. R., Dietrich, W. D., Keane, R. W., & Vaccari, J. P. D. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.583373 · Cited by 104
Grishman, E. K., White, P. C., & Savani, R. C. (2012) · Pediatric Research · doi:10.1038/pr.2012.24 · Cited by 104
A past and present overview of macrophage metabolism and functional outcomes
Curi, R., Mendes, R. D. S., Crispin, L. A. D. C., Norata, G. D., Sampaio, S. C., & Newsholme, P. (2017) · Clinical Science · doi:10.1042/cs20170220 · Cited by 103
Self-citationMachine and Deep Learning for Tuberculosis Detection on Chest X-Rays: Systematic Literature Review
Hansun, S., Argha, A., Liaw, S., Celler, B. G., & Marks, G. B. (2023) · Journal of Medical Internet Research · doi:10.2196/43154 · Cited by 133
Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?
Jefferies, C. A., Wynne, C., & Higgs, R. (2011) · Nature reviews. Immunology · doi:10.1038/nri3043 · Cited by 103
Du, R., Wu, F.-F., Lu, M., Shu, X.-D., Ding, J.-H., Wu, G., & Hu, G. (2016) · Redox Biology · doi:10.1016/j.redox.2016.08.006 · Cited by 100
Hofbauer, D., Mougiakakos, D., Broggini, L., Zaiss, M., Büttner-Herold, M., Bach, C., Spriewald, B., Neumann, F., Bisht, S., Nolting, J., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.07.002 · Cited by 100
Xu, H., Chen, J., Chen, P., Li, W., Shao, J., Hong, S., Wang, Y., Chen, L., Luo, W., & Liang, G. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.09.014 · Cited by 104
Amylin at the interface between metabolic and neurodegenerative disorders
Lutz, T. A., & Meyer, U. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00216 · Cited by 97
“Increased inflammatory processes in general, and overproduction of IL-1β in particular, may represent another important mechanism by which amylin aggregation can cause β-cell death (Masters et al., 2010; Donath and Shoelson, 2011; Westwell-Roper et al., 2011; Donath et al., 2013).”
BackgroundAdipose Tissue Remodeling as Homeostatic Inflammation
Itoh, M., Suganami, T., Hachiya, R., & Ogawa, Y. (2011) · International Journal of Inflammation · doi:10.4061/2011/720926 · Cited by 107
“Work in the authors’ laboratory was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Ministry of Health, Labor, and Welfare of Japan.”
BackgroundInside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis
Kulkarni, A., Muralidharan, C., May, S. C., Tersey, S. A., & Mirmira, R. G. (2022) · Endocrinology · doi:10.1210/endocr/bqac184 · Cited by 95
Metabolic stress, IAPP and islet amyloid
Montane, J., Klimek‐Abercrombie, A., Potter, K. J., Westwell‐Roper, C., & Bruce Verchere, C. (2012) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2012.01657.x · Cited by 98
“[23] showed that human IAPP aggregates activate the NLRP3 inflammasome in bone marrow-derived dendritic cells, leading to processing of proIL1β induced by other stimuli such as high glucose or oxidated low-density lipoprotein (LDL).”
BackgroundInfluentialNlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation
Bakker, P. J., Butter, L. M., Kors, L., Teske, G. J. D., Aten, J., Sutterwala, F. S., Florquin, S., & Leemans, J. C. (2013) · Kidney International · doi:10.1038/ki.2013.503 · Cited by 98
Ramadan, J. W., Steiner, S. R., O’Neill, C. M., & Nunemaker, C. S. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.08.005 · Cited by 104
TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis
Yoshihara, E. (2020) · Antioxidants · doi:10.3390/antiox9080765 · Cited by 101
“Although TXNIP-NLRP3 inflammasome axis is independent with known NLRP3 activation by oligomers of islet amyloid polypeptides (IAPP) [49] (a protein that forms amyloid deposits that has been observed during type-2 diabetes in pancreatic β cells), TXNIP-NLRP3 inflammasome axis seems”
BackgroundInfluentialSelf-citationThe role of the electron transport chain in immunity
Yin, M., & O’Neill, L. A. J. (2021) · The FASEB Journal · doi:10.1096/fj.202101161r · Cited by 102
Self-citationKamata, K., Mizukami, H., Inaba, W., Tsuboi, K., Tateishi, Y., Yoshida, T., & Yagihashi, S. (2014) · Amyloid · doi:10.3109/13506129.2014.937857 · Cited by 100
Zhao, N., Li, C.-C., Di, B., & Xu, L.-L. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102515 · Cited by 103
Ozkurede, U., & Franchi, L. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04535.x · Cited by 94
Self-citationInflammasomes and type 2 diabetes: An updated systematic review
Sepehri, Z., Kiani, Z., Afshari, M., Kohan, F., Dalvand, A., & Ghavami, S. (2017) · Immunology Letters · doi:10.1016/j.imlet.2017.10.010 · Cited by 99
Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases
Savic, S., Dickie, L. J., Battellino, M., & McDermott, M. (2011) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32834dd2d5 · Cited by 94
The NLRP3 inflammasome: Role in metabolic disorders and regulation by metabolic pathways
Jiang, D., Chen, S., Sun, R., Zhang, X., & Wang, D. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.01.034 · Cited by 95
Specific Inhibition of the NLRP3 Inflammasome as an Antiinflammatory Strategy in Cystic Fibrosis
McElvaney, O. J., Zasłona, Z., Becker-Flegler, K. A., Pålsson‐McDermott, E. M., Boland, F., Gunaratnam, C., Gulbins, E., O'Neill, L. A. J., Reeves, E. P., & McElvaney, N. G. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201905-1013oc · Cited by 97
Self-citationThe NLRP3 inflammasome regulates adipose tissue metabolism
Barra, N. G., Henriksbo, B. D., Anhê, F. F., & Schertzer, J. D. (2020) · Biochemical Journal · doi:10.1042/bcj20190472 · Cited by 93
Impaired macrophage autophagy induces systemic insulin resistance in obesity
Kang, Y.-H., Cho, M., Kim, J.-Y., Kwon, M.-S., Peak, J., Kang, S., Yoon, S., & Song, Y. (2016) · Oncotarget · doi:10.18632/oncotarget.9590 · Cited by 93
“Activation of autophagy by rapamycin or resveratrol or by treating obese mice with apocynin, a ROS blocker, improved glucose homeostasis without weight loss [1, 19-22].”
BackgroundMethodHafner‐Bratkovič, I., Benčina, M., Fitzgerald, K. A., Golenbock, D. T., & Jerala, R. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1140-0 · Cited by 92
“inflammasome is activated by amylin oligomeric fractions with molecular weight of\100 kDa [46].”
BackgroundAutophagy regulates inflammation following oxidative injury in diabetes
Wang, Y., Li, Y., Yin, J.-J., Wang, Y., Zhu, L., Xie, G., & Pan, S. (2013) · Autophagy · doi:10.4161/auto.23628 · Cited by 93
“IAPP (islet amyloid polypeptide), a protein that forms amyloid deposits in the pancreas during T2D, triggers the NLRP3 inflammasome and generates mature IL1B, which has been found to have profound effects on the function of pancreatic b cells, inducing them to undergo apoptosis.(18) An inflammatory response initiated…”
BackgroundRegulation of inflammasomes by ubiquitination
Bednash, J. S., & Mallampalli, R. K. (2016) · Cellular and Molecular Immunology · doi:10.1038/cmi.2016.15 · Cited by 95
Role of pancreatic β ‐cell death and inflammation in diabetes
Quan, W., Jo, E., & Lee, M. ‐. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12153 · Cited by 92
“The role of NLRP3-dependent inflammasome activation in diabetes or metabolic syndrome was suggested by the results that IL-1β is released by NLRP3 activation in response to high glucose [92], FFA [54] or human islet amyloid polypeptide (hIAPP) [93].”
BackgroundInfluentialGalozzi, P., Bindoli, S., Doria, A., & Sfriso, P. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102785 · Cited by 91
The role of NLRP3 inflammasome in aging and age-related diseases
Liang, R., Qi, X., Cai, Q., Niu, L., Huang, X., Zhang, D., Ling, J., Wu, Y., Chen, Y., Yang, P., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-023-00395-z · Cited by 98
“Another hallmark of T2DM is the accumulation of substantial amylin in the pancreas, which, upon uptake by macrophages and dendritic cells, activates the down-stream NLRP3 inflammasome [83] (Fig.”
BackgroundResveratrol inhibits the acetylated α-tubulin-mediated assembly of the NLRP3-inflammasome
Misawa, T., Saitoh, T., Kozaki, T., Park, S., Takahama, M., & Akira, S. (2015) · International Immunology · doi:10.1093/intimm/dxv018 · Cited by 93
Dubey, S. R., Turnbull, C., Pandey, A., Zhao, A., Kurera, M., Al-Zidan, R. N., Shen, C. X., Gautam, M., Mahajan, S., Jadhav, P. S., et al. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01354-y · Cited by 101
The fat cell senescence hypothesis
Newsholme, P., & de Bittencourt, P. I. H. (2014) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000077 · Cited by 92
Self-citationWatanabe, Y., Nagai, Y., & Takatsu, K. (2013) · Nutrients · doi:10.3390/nu5093757 · Cited by 92
“In addition, islet amyloid polypeptide (IAPP), which is accumulated in islet of T2DM patients, is also an inducer of NLRP3 activation [137].”
BackgroundSpecific inflammasomes in complex diseases
Masters, S. L. (2012) · Clinical Immunology · doi:10.1016/j.clim.2012.12.006 · Cited by 97
Self-citationGenetic risk converges on regulatory networks mediating early type 2 diabetes
Walker, J. T., Saunders, D. C., Rai, V., Chen, H., Orchard, P., Dai, C., Pettway, Y. D., Hopkirk, A. L., Reihsmann, C., Tao, Y., et al. (2023) · Nature · doi:10.1038/s41586-023-06693-2 · Cited by 92
Bram, Y., Frydman‐Marom, A., Yanai, I., Gilead, S., Shaltiel‐Karyo, R., Amdursky, N., & Gazit, E. (2014) · Scientific Reports · doi:10.1038/srep04267 · Cited by 89
Jabaut, J., Ather, J. L., Taracanova, A., Poynter, M. E., & Ckless, K. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.025 · Cited by 89
Krause, M. D. S., McClenaghan, N. H., Flatt, P. R., de Bittencourt, P. I. H., Murphy, C., & Newsholme, P. (2011) · Journal of Endocrinology · doi:10.1530/joe-11-0236 · Cited by 89
“This is induced by islet dendritic cell activation and infiltration by T-lymphocytes and macrophages, leading to microenvironmental changes, resulting in b-cell injury and death (Masters et al. 2010).”
BackgroundSelf-citationTuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development of dendritic cells
Wang, Y., Huang, G., Zeng, H., Yang, K., Lamb, R. F., & Chi, H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308905110 · Cited by 87
“In the innate immune system, mTOR and the upstream PI3K-AKT pathway have a well-established role in modulating the balance between TLR-induced production of pro- and anti-inflammatory DC cytokines, especially IL-12 and IL-10, thereby affecting DC function and immune responses (20–24).”
BackgroundInfluentialThe thioredoxin system: Balancing redox responses in immune cells and tumors
Muri, J., & Köpf, M. (2022) · European Journal of Immunology · doi:10.1002/eji.202249948 · Cited by 91
Meng, Z., Gao, M., Wang, C., Guan, S., Zhang, D., & Lu, J. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c07581 · Cited by 92
The inflammasome: in memory of Dr. Jurg Tschopp
Dagenais, M., Skeldon, A. M., & Saleh, M. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.159 · Cited by 92
Mohamed, I., Ishrat, T., Fagan, S. C., & El‐Remessy, A. B. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6126 · Cited by 88
Yang, S., Xia, C., Li, S., Du, L., Zhang, L., & Zhou, R. (2014) · Redox Biology · doi:10.1016/j.redox.2014.04.001 · Cited by 88
Current and future treatment of amyloid diseases
Ankarcrona, M., Winblad, B. G., Monteiro, C., Fearns, C., Powers, E. T., Johansson, J., Westermark, G. T., Presto, J., Ericzon, B. ‐., & Kelly, J. W. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12506 · Cited by 90
“Recently, it was shown that the inflammasome can be activated by islet amyloid [55] and that amyloid-containing islets contain more macrophages than non-amyloid-containing islets [56].”
Advances in the molecular mechanisms of NLRP3 inflammasome activators and inactivators
Liu, D., Zeng, X., Li, X., Cui, C., Hou, R., Guo, Z., Mehta, J. L., & Wang, X. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113863 · Cited by 88
Innate immune sensing of cell death in disease and therapeutics
Man, S. M., & Kanneganti, T. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01491-y · Cited by 94
“NLRP3 is highly responsive to lytic dead cell corpses 82 and DAMPs associated with cell death, notably ATP 19–22 , β-amyloids 83,84 , biglycan 85 , endogenous crystals 86,87 , free fatty acids 88 , histones 89 , mitochondrial DNA 90–92 , RNA 93,94 , and S100A8 or S100A9 (ref.”
NLRP3 inflammasome as a treatment target in atherosclerosis: A focus on statin therapy
Parsamanesh, N., Moossavi, M., Bahrami, A., Fereidouni, M., Barreto, G. E., & Sahebkar, A. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.05.006 · Cited by 87
Clinical approach to the inflammatory etiology of cardiovascular diseases
Ruscica, M., Corsini, A., Ferri, N., Banach, M., & Sirtori, C. R. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104916 · Cited by 87
Tannahill, G. M., & O'Neill, L. A. J. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.05.008 · Cited by 84
“In macrophages however in addition to glucose, the amyloid polypeptide (IAPP) which is secreted along with insulin in the pancreas, is required for Nlrp3-dependent IL-1β processing [50].”
Self-citationRole of islet β cell autophagy in the pathogenesis of diabetes
Lee, M. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.08.005 · Cited by 83
Birnbaum, Y., Bajaj, M., Qian, J., & Ye, Y. (2016) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2016-000227 · Cited by 85
Sun, W., Lu, H., Lyu, L., Yang, P., Lin, Z., Li, L., Sun, L., & Lü, D. (2019) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-019-00702-7 · Cited by 84
Pirzada, R. H., Javaid, N., & Choi, S. (2020) · Genes · doi:10.3390/genes11020131 · Cited by 84
Meier, D. T., Morcos, M., Samarasekera, T., Zraika, S., Hull, R. L., & Kahn, S. E. (2014) · Diabetologia · doi:10.1007/s00125-014-3304-y · Cited by 82
“In addition, compared with LF transgenic mice, HF transgenic mice had significantly increased islet expression of genes encoding CCL2, CXCL1, F4/80, CD11c, CASP1, IL-1β, TNF-α and IL-6.”
InfluentialSelf-citationYao, Y., Chen, S., Cao, M., Fan, X., Yang, T., Huang, Y., Song, X., Li, Y., Ye, L., Shen, N., et al. (2017) · Nature Communications · doi:10.1038/ncomms15402 · Cited by 90
Targeting inflammation in the treatment of type 2 diabetes
Donath, M. Y. (2013) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12172 · Cited by 83
“rodent islet amyloid, may activate the recruited macrophages, leading to further strong release of IL-1β [18,19] (figure 1).”
BackgroundMuri, J., Thut, H., Feng, Q., & Köpf, M. (2020) · eLife · doi:10.7554/elife.53627 · Cited by 83
“In particular, the Trx-inhibitor Txnip has been proposed to activate the NLRP3 inflammasome in response to ROS (Zhou et al., 2010), although these results remain controversial (Masters et al., 2010).”
ResultRole of the inflammasome in insulin resistance and type 2 diabetes mellitus
Lu, S., Li, Y., Qian, Z., Zhao, T., Feng, Z., Weng, X., & Yu, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1052756 · Cited by 91
“(44) found that mouse macrophages destroy lysosomes by engulfing IAPP, and this process activates the NLRP3 inflammasome to produce a series of inflammatory reactions.”
BackgroundNegative regulation of NLRP3 inflammasome signaling
Chen, S., & Sun, B. (2013) · Protein & Cell · doi:10.1007/s13238-013-2128-8 · Cited by 84
Rabolli, V., Lison, D., & Huaux, F. (2015) · Particle and Fibre Toxicology · doi:10.1186/s12989-016-0150-8 · Cited by 83
“BMDM exposed to amorphous silica nanoparticles with size ranging from 30 nm to 10 μm released more IL-1β in response to the smallest particles (30–1000 nm > 3 μm> 10 μm, when compared on a mass-based dose).”
ResultInfluentialTargeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity
Bednash, J. S., Weathington, N. M., Londino, J. D., Rojas, M. M., Gulick, D. L., Fort, R., Han, S., McKelvey, A. C., Chen, B. B., & Mallampalli, R. K. (2017) · Nature Communications · doi:10.1038/ncomms15203 · Cited by 85
Inflammasome and cytokine blocking strategies in autoinflammatory disorders
Moll, M., & Kuemmerle-Deschner, J. B. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.04.008 · Cited by 85
Kang, Y., Zhang, H., Zhao, Y., Wang, Y., Wang, W. T., He, Y., Zhang, W. K., Zhang, W., Zhu, X., Zhou, Y., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.071 · Cited by 83
The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome
Zhao, G., Jiang, K., Yang, Y.-P., Zhang, T., Wu, H., Shaukat, A., Qiu, C.-W., & Deng, G.-Z. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01916 · Cited by 69
Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly
Shi, Y., Wang, H., Zheng, M., Xu, W., Yang, Y., & Shi, F. (2019) · The FASEB Journal · doi:10.1096/fj.201901537r · Cited by 85
NLRP3 inflammasome and IL-1β pathway in type 2 diabetes and atherosclerosis: Friend or foe?
Chen, X., Zhang, D., Li, Y., Wang, W., Bei, W., & Guo, J. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105885 · Cited by 84
Zearalenone (ZEA)-induced intestinal inflammation is mediated by the NLRP3 inflammasome
Fan, W., Lv, Y., Ren, S., Shao, M., Shen, T., Huang, K., Zhou, J., Yan, L., & Song, S. (2017) · Chemosphere · doi:10.1016/j.chemosphere.2017.09.145 · Cited by 80
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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