Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Stroke | Review

NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes

Authors: Pu Hong, Ruo-Nan Gu, Feng-Xian Li, Xiao-Xing Xiong, Wen-Bin Liang, Zhi-Jian You, Hong-Fei Zhang

Published in: Journal of Neuroinflammation | Issue 1/2019

Login to get access

Abstract

The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes recent progress regarding the NLRP3 inflammasome as a potential treatment for ischemic stroke in patients with diabetes, two complicated diseases that often occur together. Stroke worsens glucose metabolism abnormalities, and the outcomes after stroke are more serious for diabetic patients compared with those without diabetes. Inflammation contributes to organ injury after ischemic stroke and diabetes. Recent research has focused on inhibiting the activation of inflammasomes and thus reducing the maturation of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Studies suggest that inhibition of NLRP3 prevents or alleviates both ischemic stroke and diabetes. Targeting against the assembly and activity of the NLRP3 inflammasome is a potential and novel therapy for inflammasome-associated diseases, including ischemic stroke concomitant with diabetes.
Literature
1.
Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–e492.PubMedCrossRef
2.
Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8(4):355–69.PubMedCrossRef
3.
4.
5.
Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.PubMedCrossRef
6.
Kruyt ND, Nys GM, van der Worp HB, van Zandvoort MJ, Kappelle LJ, Biessels GJ. Hyperglycemia and cognitive outcome after ischemic stroke. J Neurol Sci. 2008;270(1-2):141–7.PubMedCrossRef
7.
Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, Fineberg SE, Tierney WR. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology. 2002;59(1):67–71.PubMedCrossRef
8.
Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32(10):2426–32.CrossRefPubMed
9.
Soriano-Reixach MM, Vivanco-Hidalgo RM, Ois A, Rodriguez-Campello A, Roquer J. Interaction of sex and diabetes on outcome after ischemic stroke. Front Neurol. 2018;9:250.PubMedPubMedCentralCrossRef
10.
Luitse MJA, Biessels GJ, Rutten GEHM, Kappelle LJ. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol. 2012;11(3):261–71.CrossRefPubMed
11.
MacDougall NJ, Muir KW. Hyperglycaemia and infarct size in animal models of middle cerebral artery occlusion: systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31(3):807–18.PubMedCrossRef
12.
Tureyen K, Bowen K, Liang J, Dempsey RJ, Vemuganti R. Exacerbated brain damage, edema and inflammation in type-2 diabetic mice subjected to focal ischemia. J Neurochem. 2011;116(4):499–507.PubMedPubMedCentralCrossRef
13.
Parada E, Casas AI, Palomino-Antolin A, Gomez-Rangel V, Rubio-Navarro A, Farre-Alins V, Narros-Fernandez P, Guerrero-Hue M, Moreno JA, Rosa JM et al. Early TLR4 blockade reduces ROS and inflammation triggered by microglial pro-inflammatory phenotype in rodents and human brain ischemia models. Br J Pharmacol. 2019.
14.
15.
16.
Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.PubMedCrossRef
17.
Anon. Entrez Gene: NLRP3 NLR family, pyrin domain containing 3 [Homo sapiens (human)], Gene ID:114548.pdf. Bethesda: National Center for Biotechnology Information,National Library of Medicine; 2015.
18.
Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome:a sensor for metabolic danger? Science. 2010;327(5963):296–300.PubMedCrossRef
19.
Yang F, Wang Z, Wei X, Han H, Meng X, Zhang Y, Shi W, Li F, Xin T, Pang Q, et al. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab. 2014;34(4):660–7.PubMedPubMedCentralCrossRef
20.
Kousathana F, Georgitsi M, Lambadiari V, Giamarellos-Bourboulis EJ, Dimitriadis G, Mouktaroudi M. Defective production of interleukin-1 beta in patients with type 2 diabetes mellitus: restoration by proper glycemic control. Cytokine. 2017;90:177–84.PubMedCrossRef
21.
Gao L, Dong Q, Song Z, Shen F, Shi J, Li Y. NLRP3 inflammasome: a promising target in ischemic stroke. Inflamm Res. 2017;66(1):17–24.PubMedCrossRef
22.
Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA, et al. The NLR gene family: a standard nomenclature. Immunity. 2008;28(3):285–7.PubMedPubMedCentralCrossRef
23.
Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320(5876):674–7.PubMedPubMedCentralCrossRef
24.
Wen H, Miao EA, Ting JP. New mechanisms of NOD-like receptor-associated inflammasome activation. Immunity. 2013;39(3):432–41.PubMedCrossRef
25.
Dowling JK, O’Neill LA. Biochemical regulation of the inflammasome. Crit Rev Biochem Mol Biol. 2012;47(5):424–43.PubMedCrossRef
26.
Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10(2):417–26.PubMedCrossRef
27.
Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469(7329):221–5.PubMedCrossRef
28.
Wolf AJ, Reyes CN, Liang W, Becker C, Shimada K, Wheeler ML, Cho HC, Popescu NI, Coggeshall KM, Arditi M, et al. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan. Cell. 2016;166(3):624–36.PubMedPubMedCentralCrossRef
29.
Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88.PubMedPubMedCentralCrossRef
30.
Petrilli V, Dostert C, Muruve DA, Tschopp J. The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol. 2007;19(6):615–22.PubMedCrossRef
31.
Savic S, Dickie LJ, Wittmann M, McDermott MF. Autoinflammatory syndromes and cellular responses to stress: pathophysiology, diagnosis and new treatment perspectives. Best Pract Res Clin Rheumatol. 2012;26(4):505–33.PubMedCrossRef
32.
Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR, et al. NF-kappaB restricts inflammasome activation via elimination of damaged mitochondria. Cell. 2016;164(5):896–910.PubMedPubMedCentralCrossRef
33.
Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11(2):136–40.PubMedCrossRef
34.
Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10(3):210–5.PubMedCrossRef
35.
Hanamsagar R, Torres V, Kielian T. Inflammasome activation and IL-1beta/IL-18 processing are influenced by distinct pathways in microglia. J Neurochem. 2011;119(4):736–48.PubMedPubMedCentralCrossRef
36.
Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nunez G, Schnurr M, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61.PubMedPubMedCentralCrossRef
37.
Chen K, Zhang J, Zhang W, Zhang J, Yang J, Li K, He Y. ATP-P2X4 signaling mediates NLRP3 inflammasome activation: a novel pathway of diabetic nephropathy. Int J Biochem Cell Biol. 2013;45(5):932–43.PubMedCrossRef
38.
Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC, et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci U S A. 2009;106(48):20388–93.PubMedPubMedCentralCrossRef
39.
Cho MH, Cho K, Kang HJ, Jeon EY, Kim HS, Kwon HJ, Kim HM, Kim DH, Yoon SY. Autophagy in microglia degrades extracellular beta-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy. 2014;10(10):1761–75.PubMedPubMedCentralCrossRef
40.
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.PubMedCrossRef
41.
Li H, Willingham SB, Ting JP, Re F. Cutting Edge: inflammasome activation by Alum and Alum’s adjuvant effect are mediated by NLRP3. J Immunol. 2008;181(1):17–21.PubMedCrossRef
42.
Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14(9):1583–9.PubMedCrossRef
43.
Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12(3):222–30.PubMedCrossRef
44.
Mao K, Chen S, Chen M, Ma Y, Wang Y, Huang B, He Z, Zeng Y, Hu Y, Sun S, et al. Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Cell Res. 2013;23(2):201–12.PubMedPubMedCentralCrossRef
45.
Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, Farlik M, Decker T, Du Pasquier RA, Romero P, et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity. 2011;34(2):213–23.PubMedCrossRef
46.
Komune N, Ichinohe T, Ito M, Yanagi Y. Measles virus V protein inhibits NLRP3 inflammasome-mediated interleukin-1beta secretion. J Virol. 2011;85(24):13019–26.PubMedPubMedCentralCrossRef
47.
Bauernfeind F, Rieger A, Schildberg FA, Knolle PA, Schmid-Burgk JL, Hornung V. NLRP3 inflammasome activity is negatively controlled by miR-223. J Immunol. 2012;189(8):4175–81.PubMedCrossRef
48.
Guarda G, Dostert C, Staehli F, Cabalzar K, Castillo R, Tardivel A, Schneider P, Tschopp J. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature. 2009;460(7252):269–73.PubMedCrossRef
49.
Yu JW, Lee MS. Mitochondria and the NLRP3 inflammasome: physiological and pathological relevance. Arch Pharm Res. 2016;39(11):1503–18.PubMedCrossRef
50.
Haneklaus M, O'Neill LA, Coll RC. Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments. Curr Opin Immunol. 2013;25(1):40–5.PubMedCrossRef
51.
Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome an integrated view. Immunol Rev. 2011;243(1):136–51.PubMedCrossRef
52.
Weber K, Schilling JD. Lysosomes integrate metabolic-inflammatory cross-talk in primary macrophage inflammasome activation. J Biol Chem. 2014;289(13):9158–71.PubMedPubMedCentralCrossRef
53.
Sharma A, Tate M, Mathew G, Vince JE, Ritchie RH, de Haan JB. Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications. Front Physiol. 2018;9:114.PubMedPubMedCentralCrossRef
54.
55.
Harris J, Hartman M, Roche C, Zeng SG, O'Shea A, Sharp FA, Lambe EM, Creagh EM, Golenbock DT, Tschopp J, et al. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J Biol Chem. 2011;286(11):9587–97.PubMedPubMedCentralCrossRef
56.
57.
Abbott RD, Donahue RP, MacMahon SW, Reed DM, Yano K. Diabetes and the risk of stroke. The Honolulu Heart Program. JAMA. 1987;257(7):949–52.CrossRefPubMed
58.
59.
Bragg F, Holmes MV, Iona A, Guo Y, Du H, Chen Y, Bian Z, Yang L, Herrington W, Bennett D, et al. Association between diabetes and cause-specific mortality in rural and urban areas of China. JAMA. 2017;317(3):280–9.PubMedPubMedCentralCrossRef
60.
Yusuf S, Rangarajan S, Teo K, Islam S, Li W, Liu L, Bo J, Lou Q, Lu F, Liu T, et al. Cardiovascular risk and events in 17 low-, middle-, and high-income countries. N Engl J Med. 2014;371(9):818–27.PubMedCrossRef
61.
Collaboration ERF, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22.CrossRef
62.
Liu R, Wang H, Xu B, Chen W, Turlova E, Dong N, Sun CL, Lu Y, Fu H, Shi R, et al. Cerebrovascular safety of sulfonylureas: the role of KATP channels in neuroprotection and the risk of stroke in patients with type 2 diabetes. Diabetes. 2016;65(9):2795–809.PubMedCrossRef
63.
Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015;21(3):248–55.PubMedPubMedCentralCrossRef
64.
van Hout GP, Bosch L, Ellenbroek GH, de Haan JJ, van Solinge WW, Cooper MA, Arslan F, de Jager SC, Robertson AA, Pasterkamp G, et al. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur Heart J. 2016.
65.
Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A, Deshayes K, Lee WP, Hoffman HM, Dixit VM. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol. 2009;187(1):61–70.PubMedPubMedCentralCrossRef
66.
Fann DY, Lee SY, Manzanero S, Tang SC, Gelderblom M, Chunduri P, Bernreuther C, Glatzel M, Cheng YL, Thundyil J, et al. Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis. 2013;4:e790.PubMedCrossRef
67.
Widiapradja A, Vegh V, Lok KZ, Manzanero S, Thundyil J, Gelderblom M, Cheng YL, Pavlovski D, Tang SC, Jo DG, et al. Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways. J Neurochem. 2012;122(2):321–32.PubMedPubMedCentralCrossRef
68.
69.
Larsen CM, Faulenbach M, Vaag A, Ehses JA, Donath MY, Mandrup-Poulsen T. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32(9):1663–8.PubMedPubMedCentralCrossRef
70.
Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu JW, Meng R, Quong AA, Latz E, Scott CP, et al. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem. 2010;285(13):9792–802.PubMedPubMedCentralCrossRef
71.
He Y, Varadarajan S, Munoz-Planillo R, Burberry A, Nakamura Y, Nunez G. 3,4-methylenedioxy-beta-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J Biol Chem. 2014;289(2):1142–50.PubMedCrossRef
72.
Yan Y, Jiang W, Spinetti T, Tardivel A, Castillo R, Bourquin C, Guarda G, Tian Z, Tschopp J, Zhou R. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity. 2013;38(6):1154–63.PubMedCrossRef
73.
74.
Kim Y, Wang W, Okla M, Kang I, Moreau R, Chung S. Suppression of NLRP3 inflammasome by gamma-tocotrienol ameliorates type 2 diabetes. J Lipid Res. 2016;57(1):66–76.PubMedPubMedCentralCrossRef
75.
Honda H, Nagai Y, Matsunaga T, Okamoto N, Watanabe Y, Tsuneyama K, Hayashi H, Fujii I, Ikutani M, Hirai Y, et al. Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation. J Leukoc Biol. 2014;96(6):1087–100.PubMedCrossRef
76.
Luo B, Luo B, Wang W, Liu X, Liu X, Xia Y, Zhang C, Zhang Y, Zhang M, An F. Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model. Cardiovasc Drugs Ther. 2014;28(1):33–43.PubMedCrossRef
77.
Zhao J, Mou Y, Bernstock JD, Klimanis D, Wang S, Spatz M, Maric D, Johnson K, Klinman DM, Li X, et al. Synthetic oligodeoxynucleotides containing multiple telemeric TTAGGG motifs suppress inflammasome activity in macrophages subjected to oxygen and glucose deprivation and reduce ischemic brain injury in stroke-prone spontaneously hypertensive rats. PLoS One. 2015;10(10):e0140772.PubMedPubMedCentralCrossRef
78.
Zhang N, Zhang X, Liu X, Wang H, Xue J, Yu J, Kang N, Wang X. Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral ischemia/reperfusion in mice. Mediators Inflamm. 2014;2014:370530.PubMedPubMedCentral
79.
Yin W, Li B, Li X, Yu F, Cai Q, Zhang Z, Cheng M, Gao H. Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas. Food Funct. 2015;6(9):3065–71.PubMedCrossRef
80.
Wang X, Li R, Wang X, Fu Q, Ma S. Umbelliferone ameliorates cerebral ischemia-reperfusion injury via upregulating the PPAR gamma expression and suppressing TXNIP/NLRP3 inflammasome. Neurosci Lett. 2015;600:182–7.PubMedCrossRef
81.
Qiu J, Wang M, Zhang J, Cai Q, Lu D, Li Y, Dong Y, Zhao T, Chen H. The neuroprotection of Sinomenine against ischemic stroke in mice by suppressing NLRP3 inflammasome via AMPK signaling. Int Immunopharmacol. 2016;40:492–500.PubMedCrossRef
82.
Qin YY, Li M, Feng X, Wang J, Cao L, Shen XK, Chen J, Sun M, Sheng R, Han F, et al. Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke. Free Radic Biol Med. 2017;104:333–45.PubMedCrossRef
83.
Fann DY, Santro T, Manzanero S, Widiapradja A, Cheng YL, Lee SY, Chunduri P, Jo DG, Stranahan AM, Mattson MP, et al. Intermittent fasting attenuates inflammasome activity in ischemic stroke. Exp Neurol. 2014;257:114–9.PubMedCrossRef
84.
Tong Y, Ding ZH, Zhan FX, Cai L, Yin X, Ling JL, Ye JJ, Hou SY, Lu Z, Wang ZH, et al. The NLRP3 inflammasome and stroke. Int J Clin Exp Med. 2015;8(4):4787–94.PubMedPubMedCentral
85.
Sheu JR, Chen ZC, Jayakumar T, Chou DS, Yen TL, Lee HN, Pan SH, Hsia CH, Yang CH, Hsieh CY. A novel indication of platonin, a therapeutic immunomodulating medicine, on neuroprotection against ischemic stroke in mice. Sci Rep. 2017;7:42277.PubMedPubMedCentralCrossRef
86.
Algra A, Wermer MJ. Stroke in 2016: stroke is treatable, but prevention is the key. Nat Rev Neurol. 2017;13(2):78–9.PubMedCrossRef
87.
Arenillas JF, Alvarez-Sabin J. Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges. Cerebrovasc Dis. 2005;20(Suppl 2):75–83.PubMedCrossRef
88.
Gustin A, Kirchmeyer M, Koncina E, Felten P, Losciuto S, Heurtaux T, Tardivel A, Heuschling P, Dostert C. NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes. PLoS One. 2015;10(6):e0130624.PubMedPubMedCentralCrossRef
89.
Kim E, Tolhurst AT, Cho S. Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury. J Neuroinflammation. 2014;11:83.PubMedPubMedCentralCrossRef
90.
Fann DY, Lim YA, Cheng YL, Lok KZ, Chunduri P, Baik SH, Drummond GR, Dheen ST, Sobey CG, Jo DG, et al. Evidence that NF-kappaB and MAPK signaling promotes NLRP inflammasome activation in neurons following ischemic stroke. Mol Neurobiol. 2017.
91.
Minutoli L, Puzzolo D, Rinaldi M, Irrera N, Marini H, Arcoraci V, Bitto A, Crea G, Pisani A, Squadrito F, et al. ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury. Oxid Med Cell Longev. 2016;2016:2183026.PubMedPubMedCentralCrossRef
92.
Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke. J Neuroimmunol. 2007;184(1-2):53–68.PubMedCrossRef
93.
Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab. 2009;29(3):534–44.PubMedCrossRef
94.
Fann DY, Lee SY, Manzanero S, Chunduri P, Sobey CG, Arumugam TV. Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev. 2013;12(4):941–66.PubMedCrossRef
95.
Deroide N, Li X, Lerouet D, Van Vre E, Baker L, Harrison J, Poittevin M, Masters L, Nih L, Margaill I, et al. MFGE8 inhibits inflammasome-induced IL-1beta production and limits postischemic cerebral injury. J Clin Invest. 2013;123(3):1176–81.PubMedPubMedCentralCrossRef
96.
Hong P, Li F-X, Gu R-N, Fang Y-Y, Lai L-Y, Wang Y-W, Tao T, Xu S-Y, You Z-J, Zhang H-F. Inhibition of NLRP3 inflammasome ameliorates cerebral ischemia-reperfusion injury in diabetic mice. Neural Plasticity. 2018;2018:8.
97.
Ren H, Kong Y, Liu Z, Zang D, Yang X, Wood K, Li M, Liu Q. Selective NLRP3 (pyrin domain-containing protein 3) inflammasome inhibitor reduces brain injury after intracerebral hemorrhage. Stroke. 2018;49(1):184–92.PubMedPubMedCentralCrossRef
98.
Smith CJ, Hulme S, Vail A, Heal C, Parry-Jones AR, Scarth S, Hopkins K, Hoadley M, Allan SM, Rothwell NJ, et al. SCIL-STROKE (subcutaneous interleukin-1 receptor antagonist in ischemic stroke): a randomized controlled phase 2 trial. Stroke. 2018;49(5):1210–6.PubMedCrossRef
99.
Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162(4):597–605.PubMedCrossRef
100.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31.PubMedCrossRef
101.
Tuttolomondo A, Di Raimondo D, Pecoraro R, Maida C, Arnao V, Della Corte V, Simonetta I, Corpora F, Di Bona D, Maugeri R, et al. Early high-dosage atorvastatin treatment improved serum immune-inflammatory markers and functional outcome in acute ischemic strokes classified as large artery atherosclerotic stroke: a randomized trial. Medicine (Baltimore). 2016;95(13):e3186.CrossRef
102.
Rissanen A, Howard CP, Botha J, Thuren T, Global I. Effect of anti-IL-1beta antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14(12):1088–96.PubMedCrossRef
103.
Sloan-Lancaster J, Abu-Raddad E, Polzer J, Miller JW, Scherer JC, De Gaetano A, Berg JK, Landschulz WH. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36(8):2239–46.PubMedPubMedCentralCrossRef
104.
Wang Y, Li YB, Yin JJ, Wang Y, Zhu LB, Xie GY, Pan SH. Autophagy regulates inflammation following oxidative injury in diabetes. Autophagy. 2013;9(3):272–7.PubMedPubMedCentralCrossRef
105.
106.
Serena C, Keiran N, Ceperuelo-Mallafre V, Ejarque M, Fradera R, Roche K, Nunez-Roa C, Vendrell J, Fernandez-Veledo S. Obesity and type 2 diabetes alters the immune properties of human adipose derived stem cells. Stem Cells. 2016;34(10):2559–73.PubMedCrossRef
107.
Yong M, Kaste M. Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASS-II trial. Stroke. 2008;39(10):2749–55.PubMedCrossRef
108.
Bruno A, Saha C, Williams LS, Shankar R. IV insulin during acute cerebral infarction in diabetic patients. Neurology. 2004;62(8):1441–2.PubMedCrossRef
109.
Kruyt ND, Biessels GJ, Devries JH, Roos YB. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management. Nat Rev Neurol. 2010;6(3):145–55.PubMedCrossRef
110.
Hunt DG, Ivy JL. Epinephrine inhibits insulin-stimulated muscle glucose transport. J Appl Physiol (1985). 2002;93(5):1638–43.CrossRef
111.
Dempsey C, Rubio Araiz A, Bryson KJ, Finucane O, Larkin C, Mills EL, Robertson AA, Cooper MA, O'Neill LA, Lynch MA. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice. Brain Behav Immun. 2016.
112.
Zhai Y, Meng X, Ye T, Xie W, Sun G, Sun X. Inhibiting the NLRP3 inflammasome activation with MCC950 ameliorates diabetic encephalopathy in db/db mice. Molecules. 2018;23:3.
113.
Ward R, Li W, Abdul Y, Jackson L, Dong G, Jamil S, Filosa J, Fagan SC, Ergul A. NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia. Pharmacol Res. 2019;142:237–50.PubMedCrossRefPubMedCentral
114.
World Health Organization. Obesity, situation and trends. Geneva: World Health Organization; 2014.
115.
116.
Volpe CMO, Anjos PMF, Nogueira-Machado JA. Inflammasome as a new therapeutic target for diabetic complications. Recent Pat Endocr Metab Immune Drug Discovery. 2016;10(1):56–62.CrossRef
117.
118.
Stienstra R, Tack CJ, Kanneganti TD, Joosten LA, Netea MG. The inflammasome puts obesity in the danger zone. Cell Metab. 2012;15(1):10–8.PubMedCrossRef
119.
Sheedy FJ, Grebe A, Rayner KJ, Kalantari P, Ramkhelawon B, Carpenter SB, Becker CE, Ediriweera HN, Mullick AE, Golenbock DT, et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol. 2013;14(8):812–20.PubMedPubMedCentralCrossRef
120.
Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2012;62(1):194–204.PubMedPubMedCentralCrossRef
121.
Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, Lacroix-Desmazes S, Bayry J, Kaveri SV, Clément K, et al. T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue:relevance to obesity and type 2 diabetes. Diabetes. 2014;63(6):1966–77.PubMedCrossRef
122.
Tack CJ, Stienstra R, Joosten LAB, Netea MG. Inflammation links excess fat to insulin resistance:the role of the interleukin-1 family. Immunol Rev. 2012;249(1):239–52.PubMedCrossRef
123.
Mirza RE, Fang MM, Weinheimer-Haus EM, Ennis WJ, Koh TJ. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice. Diabetes. 2014;63(3):1103–14.PubMedPubMedCentralCrossRef
124.
Dror E, Dalmas E, Meier DT, Wueest S, Thevenet J, Thienel C, Timper K, Nordmann TM, Traub S, Schulze F, et al. Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017;18(3):283–92.PubMedCrossRef
125.
Wada J, Makino H. Innate immunity in diabetes and diabetic nephropathy. Nat Rev Nephrol. 2016;12(1):13–26.PubMedCrossRef
126.
Stienstra R, Joosten LA, Koenen T, van Tits B, van Diepen JA, van den Berg SA, Rensen PC, Voshol PJ, Fantuzzi G, Hijmans A, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 2010;12(6):593–605.PubMedPubMedCentralCrossRef
127.
Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015;4:296–307.PubMedPubMedCentralCrossRef
128.
Healy NP, Kirwan AM, McArdle MA, Holohan K, Nongonierma AB, Keane D, Kelly S, Celkova L, Lyons CL, McGillicuddy FC, et al. A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling. Mol Nutr Food Res. 2016;60(11):2421–32.PubMedCrossRef
129.
Stienstra R, van Diepen JA, Tacka CJ, Zakic MH, van de Veerdonk FL, Perera D, Neale GA, Hooiveld GJ, Hijmans A, Vroegrijk I, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108(37):15324–9.PubMedPubMedCentralCrossRef
130.
131.
Youm YH, Adijiang A, Vandanmagsar B, Burk D, Ravussin A, Dixit VD. Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. Endocrinology. 2011;152(11):4039–45.PubMedPubMedCentralCrossRef
132.
Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, et al. Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome. Cell Metab. 2012;16(2):265–73.PubMedPubMedCentralCrossRef
133.
Lawlor KE, Vince JE. Ambiguities in NLRP3 inflammasome regulation: is there a role for mitochondria? Biochim Biophys Acta. 2014;1840(4):1433–40.PubMedCrossRef
134.
Xiao YD, Huang YY, Wang HX, Wu Y, Leng Y, Liu M, Sun Q, Xia ZY. Thioredoxin-interacting protein mediates NLRP3 inflammasome activation involved in the susceptibility to ischemic acute kidney injury in diabetes. Oxid Med Cell Longev. 2016;2016:2386068.PubMedPubMedCentral
135.
Ishrat T, Mohamed IN, Pillai B, Soliman S, Fouda AY, Ergul A, El-Remessy AB, Fagan SC. Thioredoxin-interacting protein: a novel target for neuroprotection in experimental thromboembolic stroke in mice. Mol Neurobiol. 2015;51(2):766–78.PubMedCrossRef
136.
Hou Y, Wang Y, He Q, Li L, Xie H, Zhao Y, Zhao J. Nrf2 inhibits NLRP3 inflammasome activation through regulating Trx1/TXNIP complex in cerebral ischemia reperfusion injury. Behav Brain Res. 2018;336:32–9.PubMedCrossRef
137.
Baldwin AG, Brough D, Freeman S. Inhibiting the inflammasome:a chemical perspective. J Med Chem. 2016;59(5):1691–710.PubMedCrossRef
Metadata
Title
NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes
Authors
Pu Hong
Ruo-Nan Gu
Feng-Xian Li
Xiao-Xing Xiong
Wen-Bin Liang
Zhi-Jian You
Hong-Fei Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1498-0

Other articles of this Issue 1/2019

Journal of Neuroinflammation 1/2019 Go to the issue

Research

Dynamic response of microglia/macrophage polarization following demyelination in mice

Research

KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis

Research

Highly glycosylated CD147 promotes hemorrhagic transformation after rt-PA treatment in diabetes: a novel therapeutic target?

Research

Interleukin-1-related activity and hypocretin-1 in cerebrospinal fluid contribute to fatigue in primary Sjögren’s syndrome

Research

Systemic administration of orexin A ameliorates established experimental autoimmune encephalomyelitis by diminishing neuroinflammation

Review

The spleen may be an important target of stem cell therapy for stroke