Login Register Cart 0
Mini-Review Article

NLRP3: A Promising Therapeutic Target for Inflammatory Bowel Disease

Author(s): Jiayu Zhang, Shuyan Zeng, Peng Wang, Youxiang Chen and Chunyan Zeng*

Volume 24, Issue 14, 2023

Published on: 08 November, 2023

Page: [1106 - 1116] Pages: 11

DOI: 10.2174/0113894501255960231101105113

Price: $65

Abstract

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an intestinal disease with complicated pathological mechanisms. The incidence of IBD has been increasing in recent years, which has a significant negative impact on the lives of patients. Therefore, it is particularly important to find new therapeutic targets and innovative drugs for the development of IBD. Recent studies have revealed that NLRP3 inflammatory vesicles can play an important role in maintaining intestinal homeostasis and sustaining the intestinal immune response in IBD. On the one hand, aberrant activation of NLRP3 inflammatory vesicles may cause excessive immune response by converting caspase-1, proIL-18, and proIL-1β to their active forms and releasing pro-inflammatory cytokines to stimulate the development and progression of IBD, and we can improve IBD by targeting blockade of NLRP3 activation. On the other hand, NLRP3 may also play an enter protective role by maintaining the homeostasis of the intestinal immune system. In this paper, we reviewed the activation mechanism of NLRP3 inflammasome, and the effects of NLRP3 inflammasome activation on IBD are discussed from two different perspectives: pathology and protection. At the same time, we listed the effects of direct inhibitors, indirect inhibitors, and natural inhibitors of NLRP3 inflammasome on IBD in combination with cutting-edge advances and clinical practice results, providing new targets and new ideas for the clinical treatment of IBD.

Keywords: Inflammatory bowel disease, NLRP3, inflammation, regulation, drugs, pro-inflammatory cytokines.

« Previous Next »
Graphical Abstract

[1]
Beard JA, Franco DL, Click BH. The burden of cost in inflammatory bowel disease: A medical economic perspective and the future of value-based care. Curr Gastroenterol Rep 2020; 22(2): 6.
[http://dx.doi.org/10.1007/s11894-020-0744-z] [PMID: 32002671]
[2]
Mehrmal S, Uppal P, Nedley N, Giesey RL, Delost GR. The global, regional, and national burden of psoriasis in 195 countries and territories, 1990 to 2017: A systematic analysis from the Global Burden of Disease Study 2017. J Am Acad Dermatol 2021; 84(1): 46-52.
[http://dx.doi.org/10.1016/j.jaad.2020.04.139] [PMID: 32376432]
[3]
Zhao M, Gönczi L, Lakatos PL, Burisch J. The burden of inflammatory bowel disease in europe in 2020. J Crohn’s Colitis 2021; 15(9): 1573-87.
[http://dx.doi.org/10.1093/ecco-jcc/jjab029] [PMID: 33582812]
[4]
de Souza HSP. Etiopathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol 2017; 33(4): 222-9.
[http://dx.doi.org/10.1097/MOG.0000000000000364] [PMID: 28402995]
[5]
Kugathasan S, Fiocchi C. Progress in basic inflammatory bowel disease research. Semin Pediatr Surg 2007; 16(3): 146-53.
[http://dx.doi.org/10.1053/j.sempedsurg.2007.04.002] [PMID: 17602969]
[6]
Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347(6): 417-29.
[http://dx.doi.org/10.1056/NEJMra020831] [PMID: 12167685]
[7]
Zhang YZ, Li YY. Inflammatory bowel disease: Pathogenesis. World J Gastroenterol 2014; 20(1): 91-9.
[http://dx.doi.org/10.3748/wjg.v20.i1.91] [PMID: 24415861]
[8]
Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13(1): 3-10.
[http://dx.doi.org/10.1016/j.autrev.2013.06.004] [PMID: 23774107]
[9]
Hisamatsu T, Ogata H, Hibi T. Innate immunity in inflammatory bowel disease: State of the art. Curr Opin Gastroenterol 2008; 24(4): 448-54.
[http://dx.doi.org/10.1097/MOG.0b013e3282ff8b0c] [PMID: 18622158]
[10]
Knutson CG, Mangerich A, Zeng Y, et al. Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease. Proc Natl Acad Sci 2013; 110(26): E2332-41.
[http://dx.doi.org/10.1073/pnas.1222669110] [PMID: 23754421]
[11]
Bortolotti P, Faure E, Kipnis E. Inflammasomes in tissue damages and immune disorders after trauma. Front Immunol 2018; 9: 1900.
[http://dx.doi.org/10.3389/fimmu.2018.01900] [PMID: 30166988]
[12]
Carty M, Guy C, Bowie AG. Detection of viral infections by innate immunity. Biochem Pharmacol 2021; 183: 114316.
[http://dx.doi.org/10.1016/j.bcp.2020.114316] [PMID: 33152343]
[13]
Deets KA, Vance RE. Inflammasomes and adaptive immune responses. Nat Immunol 2021; 22(4): 412-22.
[http://dx.doi.org/10.1038/s41590-021-00869-6] [PMID: 33603227]
[14]
Guo H, Callaway JB, Ting JPY. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat Med 2015; 21(7): 677-87.
[http://dx.doi.org/10.1038/nm.3893] [PMID: 26121197]
[15]
Krainer J, Siebenhandl S, Weinhäusel A. Systemic autoinflammatory diseases. J Autoimmun 2020; 109: 102421.
[http://dx.doi.org/10.1016/j.jaut.2020.102421] [PMID: 32019685]
[16]
Kanneganti TD, Özören N, Body-Malapel M, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 2006; 440(7081): 233-6.
[http://dx.doi.org/10.1038/nature04517] [PMID: 16407888]
[17]
Mariathasan S, Weiss DS, Newton K, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 2006; 440(7081): 228-32.
[http://dx.doi.org/10.1038/nature04515] [PMID: 16407890]
[18]
Sutterwala FS, Ogura Y, Szczepanik M, et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 2006; 24(3): 317-27.
[http://dx.doi.org/10.1016/j.immuni.2006.02.004] [PMID: 16546100]
[19]
Chen GY, Núñez G. Inflammasomes in intestinal inflammation and cancer. Gastroenterology 2011; 141(6): 1986-99.
[http://dx.doi.org/10.1053/j.gastro.2011.10.002] [PMID: 22005480]
[20]
Bou-Dargham MJ, Khamis ZI, Cognetta AB, Sang QXA. The role of interleukin-1 in inflammatory and malignant human skin diseases and the rationale for targeting interleukin-1 Alpha. Med Res Rev 2017; 37(1): 180-216.
[http://dx.doi.org/10.1002/med.21406] [PMID: 27604144]
[21]
Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol 2017; 17(4): 219-32.
[http://dx.doi.org/10.1038/nri.2017.7] [PMID: 28260787]
[22]
Ralston JC, Lyons CL, Kennedy EB, Kirwan AM, Roche HM. Fatty acids and nlrp3 inflammasome-mediated inflammation in metabolic tissues. Annu Rev Nutr 2017; 37(1): 77-102.
[http://dx.doi.org/10.1146/annurev-nutr-071816-064836] [PMID: 28826373]
[23]
Kanneganti TD. Inflammatory bowel disease and the NLRP3 inflammasome. N Engl J Med 2017; 377(7): 694-6.
[http://dx.doi.org/10.1056/NEJMcibr1706536] [PMID: 28813221]
[24]
Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol 2021; 18(9): 2114-27.
[http://dx.doi.org/10.1038/s41423-021-00740-6] [PMID: 34321623]
[25]
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int J Mol Sci 2019; 20(13): 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572]
[26]
Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov 2018; 17(8): 588-606.
[http://dx.doi.org/10.1038/nrd.2018.97] [PMID: 30026524]
[27]
Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: A review. Front Pharmacol 2015; 6: 262.
[http://dx.doi.org/10.3389/fphar.2015.00262] [PMID: 26594174]
[28]
Zhen Y, Zhang H. NLRP3 inflammasome and inflammatory bowel disease. Front Immunol 2019; 10: 276.
[http://dx.doi.org/10.3389/fimmu.2019.00276] [PMID: 30873162]
[29]
Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 2004; 20(3): 319-25.
[http://dx.doi.org/10.1016/S1074-7613(04)00046-9] [PMID: 15030775]
[30]
Lu A, Magupalli VG, Ruan J, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 2014; 156(6): 1193-206.
[http://dx.doi.org/10.1016/j.cell.2014.02.008] [PMID: 24630722]
[31]
Zhang XN, Yu ZL, Chen JY, et al. The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis. Pharmacol Res 2022; 181: 106289.
[http://dx.doi.org/10.1016/j.phrs.2022.106289] [PMID: 35671922]
[32]
Donovan C, Liu G, Shen S, et al. The role of the microbiome and the NLRP3 inflammasome in the gut and lung. J Leukoc Biol 2020; 108(3): 925-35.
[http://dx.doi.org/10.1002/JLB.3MR0720-472RR] [PMID: 33405294]
[33]
Kobayashi K, Inohara N, Hernandez LD, et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 2002; 416(6877): 194-9.
[http://dx.doi.org/10.1038/416194a] [PMID: 11894098]
[34]
Yoo NJ, Park WS, Kim SY, et al. Corrigendum to “Nod 1, a CARD protein, enhances pro-interleukin-1 beta processing through the interaction with pro-caspase-1” [Biochem. Biophys. Res. Commun. 299(4) (2002) 652–8]. Biochem Biophys Res Commun 2021; 543: 97.
[http://dx.doi.org/10.1016/j.bbrc.2021.01.063] [PMID: 33518282]
[35]
Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM, Núñez G. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 2013; 38(6): 1142-53.
[http://dx.doi.org/10.1016/j.immuni.2013.05.016] [PMID: 23809161]
[36]
Xu Q, Zhou X, Strober W, Mao L. Inflammasome regulation: Therapeutic potential for inflammatory bowel disease. Molecules 2021; 26(6): 1725.
[http://dx.doi.org/10.3390/molecules26061725] [PMID: 33808793]
[37]
Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR. Pattern Recognition Receptors and the Host Cell Death Molecular Machinery. Front Immunol 2018; 9: 2379.
[http://dx.doi.org/10.3389/fimmu.2018.02379] [PMID: 30459758]
[38]
Zheng D, Liwinski T, Elinav E. Inflammasome activation and regulation: Toward a better understanding of complex mechanisms. Cell Discov 2020; 6(1): 36.
[http://dx.doi.org/10.1038/s41421-020-0167-x] [PMID: 32550001]
[39]
Bauernfeind FG, Horvath G, Stutz A, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 2009; 183(2): 787-91.
[http://dx.doi.org/10.4049/jimmunol.0901363] [PMID: 19570822]
[40]
Ngui IQH, Perera AP, Eri R. Does NLRP3 inflammasome and aryl hydrocarbon receptor play an interlinked role in bowel inflammation and colitis-associated colorectal cancer? Molecules 2020; 25(10): 2427.
[http://dx.doi.org/10.3390/molecules25102427] [PMID: 32456012]
[41]
Yalcinkaya M, Liu W, Islam MN, et al. Modulation of the NLRP3 inflammasome by Sars-CoV-2 Envelope protein. Sci Rep 2021; 11(1): 24432.
[http://dx.doi.org/10.1038/s41598-021-04133-7] [PMID: 34952919]
[42]
Groslambert M, Py B. Spotlight on the NLRP3 inflammasome pathway. J Inflamm Res 2018; 11: 359-74.
[http://dx.doi.org/10.2147/JIR.S141220] [PMID: 30288079]
[43]
He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 2016; 41(12): 1012-21.
[http://dx.doi.org/10.1016/j.tibs.2016.09.002] [PMID: 27669650]
[44]
Tschopp J, Schroder K. NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 2010; 10(3): 210-5.
[http://dx.doi.org/10.1038/nri2725] [PMID: 20168318]
[45]
Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 2019; 10(2): 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589]
[46]
Tait SWG, Green DR. Mitochondria and cell signalling. J Cell Sci 2012; 125(4): 807-15.
[http://dx.doi.org/10.1242/jcs.099234] [PMID: 22448037]
[47]
Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469(7329): 221-5.
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[48]
Berenbaum MR. Proceedings of the national academy of sciences-its evolution and adaptation. Proc Natl Acad Sci 2019; 116(3): 704-6.
[http://dx.doi.org/10.1073/pnas.1821201116]
[49]
Murakami T, Ockinger J, Yu J, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci USA 2012; 109(28): 11282-7.
[http://dx.doi.org/10.1073/pnas.1117765109] [PMID: 22733741]
[50]
Hornung V, Latz E. Critical functions of priming and lysosomal damage for NLRP3 activation. Eur J Immunol 2010; 40(3): 620-3.
[http://dx.doi.org/10.1002/eji.200940185] [PMID: 20201015]
[51]
Mitoma H, Hanabuchi S, Kim T, et al. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 2013; 39(1): 123-35.
[http://dx.doi.org/10.1016/j.immuni.2013.07.001] [PMID: 23871209]
[52]
Liu L, Dong Y, Ye M, et al. The Pathogenic Role of NLRP3 inflammasome activation in inflammatory bowel diseases of both mice and humans. J Crohn’s Colitis 2016; 11(6): jjw219.
[http://dx.doi.org/10.1093/ecco-jcc/jjw219] [PMID: 27993998]
[53]
Perera AP, Kunde D, Eri R. NLRP3 inhibitors as potential therapeutic agents for treatment of inflammatory bowel disease. Curr Pharm Des 2017; 23(16): 2321-7.
[http://dx.doi.org/10.2174/1381612823666170201162414] [PMID: 28155620]
[54]
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.
[http://dx.doi.org/10.4049/jimmunol.1201516] [PMID: 22984082]
[55]
Cario E. Heads up! How the intestinal epithelium safeguards mucosal barrier immunity through the inflammasome and beyond. Curr Opin Gastroenterol 2010; 26(6): 583-90.
[http://dx.doi.org/10.1097/MOG.0b013e32833d4b88] [PMID: 20664345]
[56]
Chung Y, Chang SH, Martinez GJ, et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 2009; 30(4): 576-87.
[http://dx.doi.org/10.1016/j.immuni.2009.02.007] [PMID: 19362022]
[57]
Shaw PJ, McDermott MF, Kanneganti TD. Inflammasomes and autoimmunity. Trends Mol Med 2011; 17(2): 57-64.
[http://dx.doi.org/10.1016/j.molmed.2010.11.001] [PMID: 21163704]
[58]
Nowarski R, Jackson R, Gagliani N, et al. Epithelial IL-18 equilibrium controls barrier function in colitis. Cell 2015; 163(6): 1444-56.
[http://dx.doi.org/10.1016/j.cell.2015.10.072] [PMID: 26638073]
[59]
Yao X, Zhang C, Xing Y, et al. Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis. Nat Commun 2017; 8(1): 1896.
[http://dx.doi.org/10.1038/s41467-017-01917-2] [PMID: 29196621]
[60]
Kitajima S, Takuma S, Morimoto M. Changes in colonic mucosal permeability in mouse colitis induced with dextran sulfate sodium. Exp Anim 1999; 48(3): 137-43.
[http://dx.doi.org/10.1538/expanim.48.137] [PMID: 10480018]
[61]
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004; 118(2): 229-41.
[http://dx.doi.org/10.1016/j.cell.2004.07.002] [PMID: 15260992]
[62]
Bauer C, Duewell P, Mayer C, et al. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 2010; 59(9): 1192-9.
[http://dx.doi.org/10.1136/gut.2009.197822] [PMID: 20442201]
[63]
Song Y, Zhao Y, Ma Y, et al. Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease. Cytokine Growth Factor Rev 2021; 60: 61-75.
[http://dx.doi.org/10.1016/j.cytogfr.2021.03.003] [PMID: 33773897]
[64]
Villani AC, Lemire M, Fortin G, et al. Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet 2009; 41(1): 71-6.
[http://dx.doi.org/10.1038/ng.285] [PMID: 19098911]
[65]
Allen IC, TeKippe EM, Woodford RMT, et al. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 2010; 207(5): 1045-56.
[http://dx.doi.org/10.1084/jem.20100050] [PMID: 20385749]
[66]
Dupaul-Chicoine J, Yeretssian G, Doiron K, et al. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 2010; 32(3): 367-78.
[http://dx.doi.org/10.1016/j.immuni.2010.02.012] [PMID: 20226691]
[67]
Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 2010; 32(3): 379-91.
[http://dx.doi.org/10.1016/j.immuni.2010.03.003] [PMID: 20303296]
[68]
Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti TD. IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J Immunol 2010; 185(8): 4912-20.
[http://dx.doi.org/10.4049/jimmunol.1002046] [PMID: 20855874]
[69]
Lebeis SL, Powell KR, Merlin D, Sherman MA, Kalman D. Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun 2009; 77(2): 604-14.
[http://dx.doi.org/10.1128/IAI.00907-08] [PMID: 19075023]
[70]
H T, T K, A O, et al. Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice. Scand J Gastroenterol 2003; 38(8): 837-44.
[http://dx.doi.org/10.1080/00365520310004047] [PMID: 12940437]
[71]
McKee AS, Munks MW, MacLeod MKL, et al. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol 2009; 183(7): 4403-14.
[http://dx.doi.org/10.4049/jimmunol.0900164] [PMID: 19734227]
[72]
van Heel DA, Ghosh S, Butler M, et al. Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn’s disease. Lancet 2005; 365(9473): 1794-6.
[http://dx.doi.org/10.1016/S0140-6736(05)66582-8] [PMID: 15910952]
[73]
Próchnicki T, Latz E. Inflammasomes on the crossroads of innate immune recognition and metabolic control. Cell Metab 2017; 26(1): 71-93.
[http://dx.doi.org/10.1016/j.cmet.2017.06.018] [PMID: 28683296]
[74]
Sivaprakasam S, Prasad PD, Singh N. Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol Ther 2016; 164: 144-51.
[http://dx.doi.org/10.1016/j.pharmthera.2016.04.007] [PMID: 27113407]
[75]
Rehaume LM, Jouault T, Chamaillard M. Lessons from the inflammasome: A molecular sentry linking Candida and Crohn’s disease. Trends Immunol 2010; 31(5): 171-5.
[http://dx.doi.org/10.1016/j.it.2010.01.007] [PMID: 20149741]
[76]
Cheng J, Xue F, Zhang M, et al. TRIM31 deficiency is associated with impaired glucose metabolism and disrupted gut microbiota in mice. Front Physiol 2018; 9: 24.
[http://dx.doi.org/10.3389/fphys.2018.00024] [PMID: 29497383]
[77]
Cypryk W, Nyman TA, Matikainen S. From Inflammasome to Exosome—Does Extracellular Vesicle Secretion Constitute an Inflammasome-Dependent Immune Response? Front Immunol 2018; 9: 2188.
[http://dx.doi.org/10.3389/fimmu.2018.02188] [PMID: 30319640]
[78]
Lin CK, Kazmierczak BI. Inflammation: A double-edged sword in the response to <b><i>pseudomonas aeruginosa</i></b> infection. J Innate Immun 2017; 9(3): 250-61.
[http://dx.doi.org/10.1159/000455857] [PMID: 28222444]
[79]
Vasconcelos DP, Águas AP, Barbosa MA, Pelegrín P, Barbosa JN. The inflammasome in host response to biomaterials: Bridging inflammation and tissue regeneration. Acta Biomater 2019; 83: 1-12.
[http://dx.doi.org/10.1016/j.actbio.2018.09.056] [PMID: 30273748]
[80]
Awad F, Assrawi E, Louvrier C, et al. Inflammasome biology, molecular pathology and therapeutic implications. Pharmacol Ther 2018; 187: 133-49.
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.011] [PMID: 29466702]
[81]
Hayward JA, Mathur A, Ngo C, Man SM. Cytosolic recognition of microbes and pathogens: Inflammasomes in action. Microbiol Mol Biol Rev 2018; 82(4): e00015-18.
[http://dx.doi.org/10.1128/MMBR.00015-18] [PMID: 30209070]
[82]
Henderson J, Bhattacharyya S, Varga J, O’Reilly S. Targeting TLRs and the inflammasome in systemic sclerosis. Pharmacol Ther 2018; 192: 163-9.
[http://dx.doi.org/10.1016/j.pharmthera.2018.08.003] [PMID: 30081049]
[83]
Rathinam VAK, Chan FKM. Inflammasome, inflammation, and tissue homeostasis. Trends Mol Med 2018; 24(3): 304-18.
[http://dx.doi.org/10.1016/j.molmed.2018.01.004] [PMID: 29433944]
[84]
Wu D, Chen Y, Sun Y, et al. Target of MCC950 in inhibition of nlrp3 inflammasome activation: a literature review. Inflammation 2020; 43(1): 17-23.
[http://dx.doi.org/10.1007/s10753-019-01098-8] [PMID: 31646445]
[85]
Perera AP, Fernando R, Shinde T, et al. MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Sci Rep 2018; 8(1): 8618.
[http://dx.doi.org/10.1038/s41598-018-26775-w] [PMID: 29872077]
[86]
Sharma D, Kanneganti TD. Inflammatory cell death in intestinal pathologies. Immunol Rev 2017; 280(1): 57-73.
[http://dx.doi.org/10.1111/imr.12602] [PMID: 29027223]
[87]
Oizumi T, Mayanagi T, Toya Y, Sugai T, Matsumoto T, Sobue K. NLRP3 inflammasome inhibitor OLT1177 suppresses onset of inflammation in mice with dextran sulfate sodium-induced colitis. Dig Dis Sci 2022; 67(7): 2912-21.
[http://dx.doi.org/10.1007/s10620-021-07184-y] [PMID: 34345943]
[88]
Sun K, Wang J, Lan Z, et al. Sleeve gastroplasty combined with the nlrp3 inflammasome inhibitor cy-09 reduces body weight, improves insulin resistance and alleviates hepatic steatosis in mouse model. Obes Surg 2020; 30(9): 3435-43.
[http://dx.doi.org/10.1007/s11695-020-04571-8] [PMID: 32266697]
[89]
Wang X, Sun K, Zhou Y, et al. NLRP3 inflammasome inhibitor CY-09 reduces hepatic steatosis in experimental NAFLD mice. Biochem Biophys Res Commun 2021; 534: 734-9.
[http://dx.doi.org/10.1016/j.bbrc.2020.11.009] [PMID: 33213837]
[90]
Jiang H, He H, Chen Y, et al. Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J Exp Med 2017; 214(11): 3219-38.
[http://dx.doi.org/10.1084/jem.20171419] [PMID: 29021150]
[91]
He Y, Varadarajan S, Muñoz-Planillo R, Burberry A, Nakamura Y, Núñez G. 3,4-methylenedioxy-β-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J Biol Chem 2014; 289(2): 1142-50.
[http://dx.doi.org/10.1074/jbc.M113.515080] [PMID: 24265316]
[92]
Jang J, Kwok B, Zhong H, et al. Alvimopan for the prevention of postoperative ileus in inflammatory bowel disease patients. Dig Dis Sci 2020; 65(4): 1164-71.
[http://dx.doi.org/10.1007/s10620-019-05839-5] [PMID: 31522323]
[93]
McSorley ST, Horgan PG, McMillan DC. The impact of preoperative corticosteroids on the systemic inflammatory response and postoperative complications following surgery for gastrointestinal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2016; 101: 139-50.
[http://dx.doi.org/10.1016/j.critrevonc.2016.03.011] [PMID: 26997303]
[94]
McSorley ST, Roxburgh CSD, Horgan PG, McMillan DC. The impact of preoperative dexamethasone on the magnitude of the postoperative systemic inflammatory response and complications following surgery for colorectal cancer. Ann Surg Oncol 2017; 24(8): 2104-12.
[http://dx.doi.org/10.1245/s10434-017-5817-3] [PMID: 28251379]
[95]
Pellegrini C, Fornai M, Colucci R, et al. A comparative study on the efficacy of NLRP3 inflammasome signaling inhibitors in a pre-clinical model of bowel inflammation. Front Pharmacol 2018; 9: 1405.
[http://dx.doi.org/10.3389/fphar.2018.01405] [PMID: 30559669]
[96]
Zhang T, Xu Y, Yao Y, et al. Randomized controlled trial: Perioperative dexamethasone reduces excessive postoperative inflammatory response and ileus after surgery for inflammatory bowel disease. Inflamm Bowel Dis 2021; 27(11): 1756-65.
[http://dx.doi.org/10.1093/ibd/izab065] [PMID: 33749741]
[97]
Kesisoglou F, Zimmermann EM. Novel drug delivery strategies for the treatment of inflammatory bowel disease. Expert Opin Drug Deliv 2005; 2(3): 451-63.
[http://dx.doi.org/10.1517/17425247.2.3.451] [PMID: 16296767]
[98]
Colman RJ, Lawton RC, Dubinsky MC, Rubin DT. Methotrexate for the treatment of pediatric crohn’s disease: A systematic review and meta-analysis. Inflamm Bowel Dis 2018; 24(10): 2135-41.
[http://dx.doi.org/10.1093/ibd/izy078] [PMID: 29688409]
[99]
Pang Z, Wang G, Ran N, et al. Inhibitory effect of methotrexate on rheumatoid arthritis inflammation and comprehensive metabolomics analysis using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-Q/TOF-MS). Int J Mol Sci 2018; 19(10): 2894.
[http://dx.doi.org/10.3390/ijms19102894] [PMID: 30249062]
[100]
Mantzaris GJ. Thiopurines and methotrexate use in ibd patients in a biologic era. Curr Treat Options Gastroenterol 2017; 15(1): 84-104.
[http://dx.doi.org/10.1007/s11938-017-0128-0] [PMID: 28160250]
[101]
Antonioli L, Fornai M, Colucci R, et al. The blockade of adenosine deaminase ameliorates chronic experimental colitis through the recruitment of adenosine A2A and A3 receptors. J Pharmacol Exp Ther 2010; 335(2): 434-42.
[http://dx.doi.org/10.1124/jpet.110.171223] [PMID: 20668053]
[102]
Lamkanfi M, Mueller JL, Vitari AC, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol 2009; 187(1): 61-70.
[http://dx.doi.org/10.1083/jcb.200903124] [PMID: 19805629]
[103]
Marchetti C, Chojnacki J, Toldo S, et al. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J Cardiovasc Pharmacol 2014; 63(4): 316-22.
[http://dx.doi.org/10.1097/FJC.0000000000000053] [PMID: 24336017]
[104]
Marchetti C, Toldo S, Chojnacki J, et al. Pharmacologic inhibition of the NLRP3 inflammasome preserves cardiac function after ischemic and nonischemic injury in the mouse. J Cardiovasc Pharmacol 2015; 66(1): 1-8.
[http://dx.doi.org/10.1097/FJC.0000000000000247] [PMID: 25915511]
[105]
Liu W, Guo W, Wu J, et al. A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem Pharmacol 2013; 85(10): 1504-12.
[http://dx.doi.org/10.1016/j.bcp.2013.03.008] [PMID: 23506741]
[106]
He X, Wei Z, Wang J, et al. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis. Sci Rep 2016; 6(1): 28370.
[http://dx.doi.org/10.1038/srep28370] [PMID: 27321991]
[107]
Cao H, Liu J, Shen P, et al. Protective effect of naringin on dss-induced ulcerative colitis in Mice. J Agric Food Chem 2018; 66(50): 13133-40.
[http://dx.doi.org/10.1021/acs.jafc.8b03942] [PMID: 30472831]
[108]
Sun Y, Zhao Y, Yao J, et al. Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation. Biochem Pharmacol 2015; 94(2): 142-54.
[http://dx.doi.org/10.1016/j.bcp.2015.02.002] [PMID: 25677765]
[109]
Chen L, You Q, Hu L, et al. The antioxidant procyanidin reduces reactive oxygen species signaling in macrophages and ameliorates experimental colitis in mice. Front Immunol 2018; 8: 1910.
[http://dx.doi.org/10.3389/fimmu.2017.01910] [PMID: 29354126]
[110]
Kong F, Ye B, Cao J, et al. Curcumin represses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB and P2X7R signaling in pma-induced macrophages. Front Pharmacol 2016; 7: 369.
[http://dx.doi.org/10.3389/fphar.2016.00369] [PMID: 27777559]
[111]
Yang N, Xia Z, Shao N, et al. Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway. Sci Rep 2017; 7(1): 11036.
[http://dx.doi.org/10.1038/s41598-017-11408-5] [PMID: 28887507]
[112]
Gong Z, Zhao S, Zhou J, et al. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production. Mol Immunol 2018; 104: 11-9.
[http://dx.doi.org/10.1016/j.molimm.2018.09.004] [PMID: 30396035]
[113]
He H, Jiang H, Chen Y, et al. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat Commun 2018; 9(1): 2550.
[http://dx.doi.org/10.1038/s41467-018-04947-6] [PMID: 29959312]

Rights & Permissions Print Cite
Article Metrics
49
2
© 2024 Bentham Science Publishers | Privacy Policy