Inflammasomes: Role in disease pathogenesis and therapeutic potential

66. Broz P., Monack D.M. Molecular mechanisms of inflammasome activation during microbial infections. Immunol. Rev., 2011, vol. 243, no. 1, pp. 174–190. doi: 10.1111/j.1600-065X.2011.01041.x.

67.   Fernandes-Alnemri T., Kang S., Anderson C., Sagara J., Fitzgerald K.A., Alnemri E.S. Cutting edge: TLR signaling licenses IRAK1 for rapid activation of the NLRP3 inflammasome. J. Immunol., 2013, vol. 191, no. 8, pp. 3995–3999. doi: 10.4049/jimmunol.1301681.

68.   Juliana C., Fernandes-Alnemri T., Kang S., Farias A., Qin F., Alnemri E.S. Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J. Biol. Chem., 2012, vol. 287, no. 43, pp. 36617–36622. doi: 10.1074/jbc.M112.407130.

69.   Muñoz-Planillo R., Kuffa P., Martínez-Colón G., Smith B.L., Rajendiran T.M., Nuñez G. K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity, 2013, vol. 38, no. 6, pp. 1142–1153. doi: 10.1016/j.immuni.2013.05.016.

70. Kahlenberg J.M., Lundberg K.C., Kertesy S.B., Qu Y., Dubyak G.R. Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-κβ-driven protein synthesis. J. Immunol., 2005, vol. 175, no. 11, pp. 7611–7622. doi: 10.4049/jimmunol.175.11.7611.

71.   Ferrari D., Chiozzi P., Falzoni S., Dal Susino M., Melchiorri L., Baricordi O.R., Di Virgilio F. Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. J. Immunol., 1997, vol. 159, no. 3, pp. 1451–1458.

72.   Perregaux D., Gabel C.A. Interleukin-1β maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. J. Biol. Chem., 1994, vol. 269, no. 21, pp. 15195–15203.

73.   Ghonime M.G., Shamaa O.R., Das S., Eldomany R.A., Fernandes-Alnemri T., Alnemri E.S., Gavrilin M.A., Wewers M.D. Inflammasome priming by lipopolysaccharide is dependent upon ERK signaling and proteasome function. J. Immunol., 2014, vol. 192, no. 8, pp. 3881–3888. doi: 10.4049/jimmunol.1301974.

74.   Liu X., Zhang Z., Ruan J., Pan Y., Magupalli V.G., Wu H., Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 2016, vol. 535, no. 7610, pp. 153–158. doi: 10.1038/nature18629.

75.   Shi J., Zhao Y., Wang K., Shi X., Wang Y., Huang H., Zhuang Y., Cai T., Wang F., Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature, 2015, vol. 526, no. 7575, pp. 660–665. doi: 10.1038/nature15514.

76.   Man S.M., Hopkins L.J., Nugent E., Cox S., Gluck I.M., Tourlomousis P., Wright J.A., Cicuta P., Monie T.P., Bryant C.E. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc. Natl. Acad. Sci. U. S. A., 2014, vol. 111, no. 20, pp. 7403–7408. doi: 10.1073/pnas.1402911111.

77.   Chen G.Y., Liu M., Wang F., Bertin J., Nunez G. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J. Immunol., 2011, vol. 186, no. 12, pp. 7187–7194. doi: 10.4049/jimmunol.1100412.

78.   Grenier J.M., Wang L., Manji G.A., Huang W.J., Al-Garawi A., Kelly R., Carlson A., Merriam S., Lora J.M., Briskin M., DiStefano P.S., Bertin J. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-κβ and caspase-1. FEBS Lett., 2002, vol. 530, nos. 1–3, pp. 73–78. doi: 10.1016/S0014-5793(02)03416-6.

79.   Normand S., Delanoye-Crespin A., Bressenot A., Huot L., Grandjean T., Peyrin-Biroulet L., Lemoine Y., Hot D., Chamaillard M. Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. Proc. Natl. Acad. Sci. U. S. A., 2011, vol. 108, no. 23, pp. 9601–9606. doi: 10.1073/pnas.1100981108.

80.   Anand P.K., Malireddi R.K., Lukens J.R., Vogel P., Bertin J., Lamkanfi M., Kanneganti T.D. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature, 2012, vol. 488, no. 7411, pp. 389–393. doi: 10.1038/nature11250.

81.   Wlodarska M., Thaiss C.A., Nowarski R., Henao-Mejia J., Zhang J.P., Brown E.M., Frankel G., Levy M., Katz M.N., Philbrick W.M., Elinav E., Finlay B.B., Flavell R.A. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell, 2014, vol. 156, no. 5, pp. 1045–1059. doi: 10.1016/j.cell.2014.01.026.

82.   Levy M., Shapiro H., Thaiss C.A., Elinav E. NLRP6: A multifaceted innate immune sensor. Trends Immunol., 2017, vol. 38, no. 4, pp. 248–260. doi: 10.1016/j.it.2017.01.001.

83.   Wang P., Zhu S., Yang L., Cui S., Pan W., Jackson R., Zheng Y., Rongvaux A., Sun Q., Yang G., Gao S., Lin R.,. You F, Flavell R., Fikrig E. Nlrp6 regulates intestinal antiviral innate immunity. Science, 2015, vol. 350, no. 6262, pp. 826-830. doi: 10.1126/science.aab3145.

84.   Mamantopoulos M., Ronchi F., McCoy K.D., Wullaert A. Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions. Gut Microbes, 2018, vol. 9, no. 4, pp. 374–381. doi: 10.1080/19490976.2017.1421888.

85.   Levy M., Thaiss C.A., Zeevi D., Dohnalova L., Zilberman-Schapira G., Mahdi J.A., David E., Savidor A., Korem T., Herzig Y., Pevsner-Fischer M., Shapiro H., Christ A., Harmelin A., Halpern Z., Latz E., Flavell R.A., Amit I., Segal E., Elinav E. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell, 2015, vol. 163, no. 6, pp. 1428–1443. doi: 10.1016/j.cell.2015.10.048.

86.   Birchenough G.M., Nystrom E.E., Johansson M.E., Hansson G.C. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science, 2016, vol. 352, no. 6293, pp. 1535–1542. doi: 10.1126/science.aaf7419.

87.   Shen C., Lu A., Xie W.J., Ruan J., Negro R., Egelman E.H., Fu T.M., Wu H. Molecular mechanism for NLRP6 inflammasome assembly and activation. Proc. Natl. Acad. Sci. U. S. A., 2019, vol. 116, no. 6, pp. 2052–2057. doi: 10.1073/pnas.1817221116.

88.   Lu A., Magupalli V.G., Ruan J., Yin Q., Atianand M.K., Vos M.R., Schroder G.F., Fitzgerald K.A., Wu H., Egelman E.H. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell, 2014, vol. 156, no. 6, pp. 1193–1206. doi: 10.1016/j.cell.2014.02.008.

89.   Lu A., Li Y., Schmidt F.I., Yin Q., Chen S., Fu T.M., Tong A.B., Ploegh H.L., Mao Y., Wu H. Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism. Nat. Struct. Mol. Biol., 2016, vol. 23, no. 5, pp. 416–425. doi: 10.1038/nsmb.3199.

90.   Poyet J.L., Srinivasula S.M., Tnani M., Razmara M., Fernandes-Alnemri T., Alnemri E.S. Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J. Biol. Chem., 2001, vol. 276, no. 30, pp. 28309–28313. doi: 10.1074/jbc.C100250200.

91.   Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G., Caffrey D.R., Latz E., Fitzgerald K.A. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature, 2009, vol. 458, no. 7237, pp. 514–518. doi: 10.1038/nature07725.

92.   Zhao Y., Yang J., Shi J., Gong Y.N., Lu Q., Xu H., Liu L., Shao F. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature, 2011, vol. 477, no. 7366, pp. 596–600. doi: 10.1038/nature10510.

93.   Broz P., Newton K., Lamkanfi M., Mariathasan S., Dixit V.M., Monack D.M. Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J. Exp. Med., 2010, vol. 207, no. 8, pp. 1745–1755. doi: 10.1084/jem.20100257.

94.   Van Opdenbosch N., Gurung P., Walle L. V., Fossoul A., Kanneganti T.-D., Lamkanfi M. Activation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation. Nat. Commun., 2014, vol. 5, art. 3209. doi: 10.1038/ncomms4209.

95.   Lamkanfi M., Dixit V.M. Mechanisms and functions of inflammasomes. Cell, 2014, vol. 157, no. 5, pp. 1013–1022. doi: 10.1016/j.cell.2014.04.007.

96.   Lamkanfi M., Amer A., Kanneganti T.-D., Muñoz-Planillo R., Chen G., Vandenabeele P., Fortier A., Gros P., Núñez G. The Nod-like receptor family member Naip5/Birc1e restricts Legionella pneumophila growth independently of caspase-1 activation. J. Immunol., 2007, vol. 178, no. 12, pp. 8022–8027. doi: 10.4049/jimmunol.178.12.8022.

97.   von Moltke J., Trinidad N.J., Moayeri M., Kintzer A.F., Wang S.B., van Rooijen N., Brown C.R., Krantz B.A., Leppla S.H., Gronert K., Vance R.E. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature, 2012, vol. 490, no. 7418, pp. 107–111. doi: 10.1038/nature11351.

98.   Li Y., Fu T.M., Lu A., Witt K., Ruan J., Shen C., Wu H. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc. Natl. Acad. Sci. U. S. A., 2018, vol. 115, no. 43, pp. 10845–10852. doi: 10.1073/pnas.1810524115.

99.   Kummer J.A., Broekhuizen R., Everett H., Agostini L., Kuijk L., Martinon F., van Bruggen R., Tschopp J. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J. Histochem. Cytochem., 2007, vol. 55, no. 5, pp. 443–452. doi: 10.1369/jhc.6A7101.2006.

100.  Tran T.A.T., Grievink H.W., Lipinska K., Kluft C., Burggraaf J., Moerland M., Tasev D., Malone K.E. Whole blood assay as a model for in vitro evaluation of inflammasome activation and subsequent caspase-mediated interleukin-1 beta release. PLoS ONE, 2019, vol. 14, no. 4, art. e0214999, pp. 1–16. doi: 10.1371/journal.pone.0214999.

101.  Kany S., Horstmann J.P., Sturm R., Mors K., Relja B. Reduced NLRP3 gene expression limits the IL-1β cleavage via inflammasome in monocytes from severely injured trauma patients. Mediators Inflammation, 2018, vol. 2018, art. 1752836, pp. 1–8. doi: 10.1155/2018/1752836.

102.  Erlich  Z., Shlomovitz I., Edry-Botzer L., Cohen H., Frank D., Wang H., Lew A.M., Lawlor K.E., Zhan Y., Vince J.E., Gerlic M. Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model. Nat. Immunol., 2019, vol. 20, no. 4, pp. 397–406. doi: 10.1038/s41590-019-0313-5.

103.  Arend W.P., Palmer G., Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol. Rev., 2008, vol. 223, pp. 20–38. doi: 10.1111/j.1600-065X.2008.00624.x.

104.  Serti E., Werner J.M., Chattergoon M., Cox A.L., Lohmann V., Rehermann B. Monocytes activate natural killer cells via inflammasome-induced interleukin 18 in response to hepatitis C virus replication. Gastroenterology, 2014, vol. 147, no. 1, pp. 209–220.e3. doi: 10.1053/j.gastro.2014.03.046.

105.  Sadatomo A., Inoue Y., Ito H., Karasawa T., Kimura H., Watanabe S., Mizushina Y., Nakamura J., Kamata R., Kasahara T., Horie H., Sata N., Takahashi M. Interaction of neutrophils with macrophages promotes IL-1β maturation and contributes to hepatic ischemia–reperfusion injury. J. Immunol., 2017, vol. 199, no. 9, pp. 3306–3315. doi: 10.4049/jimmunol.1700717.

106.  Yu X., Zhang H., Yu L., Liu M., Zuo Z., Han Q., Zhang J., Tian Z., Zhang C. Intestinal lamina propria CD4⁺ T cells promote bactericidal activity of macrophages via galectin-9 and Tim-3 Interaction during Salmonella enterica serovar Typhimurium infection. Infect. Immun., 2018, vol. 86, no. 8, art. e00769-17, pp. 1–15. doi: 10.1128/IAI.00769-17.

107.  Lukens J.R., Barr M.J., Chaplin D.D., Chi H., Kanneganti T.D. Inflammasome-derived IL-1β regulates the production of GM-CSF by CD4⁺ T cells and γδ T cells. J. Immunol., 2012, vol. 188, no. 7, pp. 3107–3115. doi: 10.4049/jimmunol.1103308.

108.  Chen K.W., Monteleone M., Boucher D., Sollberger G., Ramnath D., Condon N.D., von Pein J.B., Broz P., Sweet M.J., Schroder K. Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps. Sci. Immunol., 2018, vol. 3, no. 26, art. eaar6676, pp. 1–11. doi: 10.1126/sciimmunol.aar6676.

109.  Senju H., Kumagai A., Nakamura Y., Yamaguchi H., Nakatomi K., Fukami S., Shiraishi K., Harada Y., Nakamura M., Okamura H., Tanaka Y., Mukae H. Effect of IL-18 on the expansion and phenotype of human natural killer cells: Application to cancer immunotherapy. Int. J. Biol. Sci., 2018, vol. 14, no. 3, pp. 331–340. doi: 10.7150/ijbs.22809.

110.  Chow M.T., Sceneay J., Paget C., Wong C.S., Duret H., Tschopp J., Moller A., Smyth M.J. NLRP3 suppresses NK cell-mediated responses to carcinogen-induced tumors and metastases. Cancer Res., 2012, vol. 72, no. 22, pp. 5721–5732. doi: 10.1158/0008-5472.CAN-12-0509.

111.  Lamkanfi M., Mueller J.L., Vitari A.C., Misaghi S., Fedorova A., Deshayes K., Lee W.P., Hoffman H.M., Dixit V.M. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 2009, vol. 187, no. 1, pp. 61–70. doi: 10.1083/jcb.200903124.

112.  Linton S.D. Caspase inhibitors: A pharmaceutical industry perspective. Curr. Top. Med Chem., 2005, vol. 5, no. 16, pp. 1697–1717. doi: 10.2174/156802605775009720.

113.  Cornelis S., Kersse K., Festjens N., Lamkanfi M., Vandenabeele P. Inflammatory caspases: Targets for novel therapies. Curr. Pharm. Des., 2007, vol. 13, no. 4, pp. 367–385. doi: 10.2174/138161207780163006.

114.  Boxer M.B., Quinn A.M., Shen M., Jadhav A., Leister W., Simeonov A., Auld D.S., Thomas C.J. A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety, ChemMedChem, 2010, vol. 5, no. 5, pp. 730–738. doi: 10.1002/cmdc.200900531.

115.  Wang W., Nguyen L.T., Burlak C., Chegini F., Guo F., Chataway T., Ju S., Fisher O.S., Miller D.W., Datta D., Wu F., Wu C.X., Landeru A., Wells J.A., Cookson M.R., Boxer M.B., Thomas C.J., Gai W.P., Ringe D., Petsko G.A., Hoang Q.Q. Caspase-1 causes truncation and aggregation of the Parkinson’s disease-associated protein alpha-synuclein. Proc. Natl. Acad. Sci. U. S. A., 2016, vol. 113, no. 34, pp. 9587–9592. doi: 10.1073/pnas.1610099113.

116.  Flores J., Noël A., Foveau B., Lynham J., Lecrux C., LeBlanc A.C. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model. Nat. Commun., 2018, vol. 9, no. 1, art. 3916, pp. 1–14. doi: 10.1038/s41467-018-06449-x.

117.  Zhang Y., Zheng Y. Effects and mechanisms of potent caspase-1 inhibitor VX765 treatment on collagen-induced arthritis in mice. Clin. Exp. Rheumatol., 2016, vol. 34, no. 1, pp. 111–118.

118.  McKenzie B.A., Mamik M.K., Saito L.B., Boghozian R., Monaco M.C., Major E.O., Lu J.Q., Branton W.G., Power C. Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A., 2018, vol. 115, no. 26, pp. E6065–E6074. doi: 10.1073/pnas.1722041115.

119.  Yang X.M., Downey J.M., Cohen M.V., Housley N.A., Alvarez D.F., Audia J.P. The highly selective caspase-1 inhibitor VX-765 provides additive protection against myocardial infarction in rat hearts when combined with a platelet inhibitor. J. Cardiovasc. Pharmacol. Ther., 2017, vol. 22, no. 6, pp. 574–578. doi: 10.1177/1074248417702890.

120.  Do Carmo H., Arjun S., Petrucci O., Yellon D.M., Davidson S.M. The caspase 1 inhibitor VX-765 protects the isolated rat heart via the RISK pathway. Cardiovasc. Drugs Ther., 2018, vol. 32, no. 2, pp. 165–168. doi: 10.1007/s10557-018-6781-2.

121. Audia J.P., Yang X.-M., Crockett E.S., Housley N., Haq E.U., O’Donnell K., Cohen M.V., Downey J.M., Alvarez D.F. Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y₁₂ receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function. Basic Res. Cardiol., 2018, vol. 113, no. 5, art. 32, pp. 1–15. doi: 10.1007/s00395-018-0692-z.

122.  Li Q., Dai Z., Cao Y., Wang Y. Caspase-1 inhibition mediates neuroprotection in experimental stroke by polarizing M2 microglia/macrophage and suppressing NF-κB activation. Biochem. Biophys. Res. Commun., 2019, vol. 513, no. 2, pp. 479–485. doi: 10.1016/j.bbrc.2019.03.202.

123.  Coll R.C., Robertson A.A., Chae J.J., Higgins S.C., Muñoz-Planillo R., Inserra M.C., Vetter I., Dungan L.S., Monks B.G., Stutz A., Croker D.E., Butler M.S., Haneklaus M., Sutton C.E., Núñez G., Latz E., Kastner D.L., Mills K.H., Masters S.L., Schroder K., Cooper M.A., O’Neill L.A. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med., 2015, vol. 21, no. 3, pp. 248–255. doi: 10.1038/nm.3806.

124.  Youm Y.-H., Nguyen K.Y., Grant R.W., Goldberg E.L., Bodogai M., Kim D., D’Agostino D., Planavsky N., Lupfer C., Kanneganti T.D., Kang S., Horvath T.L., Fahmy T.M., Crawford P.A., Biragyn A., Alnemri E., Dixit E. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat. Med., 2015, vol. 21, no. 3, pp. 263–269. doi: 10.1038/nm.3804.

125.  Perregaux D.G., McNiff P., Laliberte R., Hawryluk N., Peurano H., Stam E., Eggler J., Griffiths R., Dombroski M.A., Gabel C.A. Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors. J. Pharmacol. Exp. Ther., 2001, vol. 299, no. 1, pp. 187–197.

126.  Chen S., Yao L., Huang P., He Q., Guan H., Luo Y., Zou Z., Wei S., Peng G., Yan J., Chen R., Zhang Q., Tao A. Blockade of the NLRP3/caspase-1 axis ameliorates airway neutrophilic inflammation in a toluene diisocyanate-induced murine asthma model. Toxicol. Sci., 2019, vol. 170, no. 2, pp. 462–475. doi: 10.1093/toxsci/kfz099.

127.  Qu J., Yuan Z., Wang G., Wang X., Li K. The selective NLRP3 inflammasome inhibitor MCC950 alleviates cholestatic liver injury and fibrosis in mice. Int. Immunopharmacol., 2019, vol. 70, pp. 147–155. doi: 10.1016/j.intimp.2019.02.016.

128.  Ward R., Li W., Abdul Y., Jackson L., Dong G., Jamil S., Filosa J., Fagan S.C., Ergul A. NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia. Pharmacol. Res., 2019, vol. 142, pp. 237–250. doi: 10.1016/j.phrs.2019.01.035.

129.  Zhang Y., Lv X., Hu Z., Ye X., Zheng X., Ding Y., Xie P., Liu Q. Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction. Cell Death Dis., 2017, vol. 8, no. 7, art. e2941, pp. 1–9. doi: 10.1038/cddis.2017.308.

130.  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, vol. 23, no. 3, art. 522, pp. 1–14. doi: 10.3390/molecules23030522.

131.  Dempsey C., Araiz A.R., Bryson K.J., Finucane O., Larkin C., Mills E.L., Robertson A.A.B., Cooper M.A., O’Neill L.A.J., Lynch M.A. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice. Brain. Behav. Immun., 2017, vol. 61, pp. 306–316. doi: 10.1016/j.bbi.2016.12.014.

132.  van der Heijden T., Kritikou E., Venema W., van Duijn J., van Santbrink P.J., Slütter B., Foks A.C., Bot I., Kuiper J. NLRP3 inflammasome inhibition by MCC950 reduces atherosclerotic lesion development in apolipoprotein E-deficient mice-brief report. Arterioscler., Thromb., Vasc. Biol., 2017, vol. 37, no. 8, pp. 1457–1461. doi: 10.1161/ATVBAHA.117.309575.

133.  Netea M.G., Joosten L.A. Inflammasome inhibition: Putting out the fire. Cell Metab., 2015, vol. 21, no. 4, pp. 513–514. doi: 10.1016/j.cmet.2015.03.012.

134.  Shang S., Wang L., Zhang Y., Lu H., Lu X. The beta-hydroxybutyrate suppresses the migration of glioma cells by inhibition of NLRP3 inflammasome. Cell Mol. Neurobiol., 2018, vol. 38, no. 8, pp. 1479–1489. doi: 10.1007/s10571-018-0617-2.

135.  Trotta M.C., Maisto R., Guida F., Boccella S., Luongo L., Balta C., D’Amico G., Herman H., Hermenean A., Bucolo C., D’Amico M. The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome. PLoS ONE, 2019, vol. 14, no. 1, art. e0211005, pp. 1–16. doi: 10.1371/journal.pone.0211005.

136.  Chakraborty S., Galla S., Cheng X., Yeo J.Y., Mell B., Singh V., Yeoh B., Saha P., Mathew A.V., Vijay-Kumar M., Joe B. Salt-responsive metabolite, β-hydroxybutyrate, attenuates hypertension. Cell Rep., 2018, vol. 25, no. 3, pp. 677–689.e4. doi: 10.1016/j.celrep.2018.09.058.

137.  He H., Jiang H., Chen Y., Ye J., Wang A., Wang C., Liu Q., Liang G., Deng X., Jiang W., Zhou R. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat. Commun., 2018, vol. 9, no. 1, art. 2550, pp. 1–12. doi: 10.1038/s41467-018-04947-6.

138.  Bartel D.P. MicroRNAs: Target recognition and regulatory functions. Cell, 2009, vol. 136, no. 2, pp. 215–233. doi: 10.1016/j.cell.2009.01.002.

139.  Chen S., Sun B. Negative regulation of NLRP3 inflammasome signaling. Protein Cell, 2013, vol. 4, no. 4, pp. 251–258, doi: 10.1007/s13238-013-2128-8.

140.  Bauernfeind F., Rieger A., Schildberg F.A., Knolle P.A., Schmid-Burgk J.L., Hornung V. NLRP3 inflammasome activity is negatively controlled by miR-223. J. Immunol., 2012, vol. 189, no. 8, pp. 4175–4181. doi: 10.4049/jimmunol.1201516.

141.  Haneklaus M., Gerlic M., Kurowska-Stolarska M., Rainey A.A., Pich D., McInnes I.B., Hammerschmidt W., O’Neill L.A., Masters S.L. Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1β production. J. Immunol., 2012, vol. 189, no. 8, pp. 3795–3799. doi: 10.4049/jimmunol.1200312.

142.  Tezcan G., Martynova E.V., Gilazieva Z.E., McIntyre A., Rizvanov A.A., Khaiboullina S.F. MicroRNA post-transcriptional regulation of the NLRP3 inflammasome in immunopathologies. Front. Pharmacol., 2019, vol. 10, art. 451, pp. 1–22. doi: 10.3389/fphar.2019.00451.