Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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NLRP3 Inflammasome as Therapeutic Targets in Inflammatory Diseases

  • Annamneedi Venkata Prakash (Department of Pharmacy and Institute of Chronic Disease, Sahmyook University) ;
  • Il-Ho Park (Department of Pharmacy and Institute of Chronic Disease, Sahmyook University) ;
  • Jun Woo Park (Department of Pharmacy and Institute of Chronic Disease, Sahmyook University) ;
  • Jae Pil Bae (Department of Pharmacy and Institute of Chronic Disease, Sahmyook University) ;
  • Geum Seon Lee (Department of Counseling and Psychology, Sahmyook University) ;
  • Tae Jin Kang (Department of Pharmacy and Institute of Chronic Disease, Sahmyook University)
  • Received : 2023.05.22
  • Accepted : 2023.05.30
  • Published : 2023.07.01
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Abstract

Innate immunity is a first line defence system in the body which is for sensing signals of danger such as pathogenic microbes or host-derived signals of cellular stress. Pattern recognition receptors (PRR's), which present in the cell memebrane, are suspect the infection through pathogen-associated molecular patterns (PAMP), and activate innate immunity with response to promote inflammation via inflammatory cells such as macrophages and neutrophils, and cytokines. Inflammasome are protein complexes which are part of innate immunity in inflammation to remove pathogens and repair damaged tissues. What is the important role of inflammation in disease? In this review, we are focused on the action mechanism of NLRP3 inflammasome in inflammatory diseases such as asthma, atopic dermatitis, and sepsis.

Keywords

Acknowledgement

This paper was supported by the Academic Research Fund of Dr. Myung Ki (MIKE) Hong in 2021.

References

  1. Arend, W. P., Palmer, G. and Gabay, C. (2008) IL-1, IL-18, and IL-33 families of cytokines. Immunol. Rev. 223, 20-38.  https://doi.org/10.1111/j.1600-065X.2008.00624.x
  2. Bauer, C., Duewell, P., Mayer, C., Lehr, H. A., Fitzgerald, K. A., Dauer, M., Tschopp, J., Endres, S., Latz, E. and Schnurr, M. (2010) Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 59, 1192-1199.  https://doi.org/10.1136/gut.2009.197822
  3. Bauernfeind, F., Ablasser, A., Bartok, E., Kim, S., Schmid-Burgk, J., Cavlar, T. and Hornung, V. (2011a) Inflammasomes: current understanding and open questions. Cell. Mol. Life Sci. 68, 765-783.  https://doi.org/10.1007/s00018-010-0567-4
  4. Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Nunez, G. and Hornung, V. (2011b) Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J. Immunol. 187, 613-617.  https://doi.org/10.4049/jimmunol.1100613
  5. Bauernfeind, F. G., Horvath, G., Stutz, A., Alnemri, E. S., MacDonald, K., Speert, D., Fernandes-Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., Hornung, V. and Latz, E. (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183, 787-791.  https://doi.org/10.4049/jimmunol.0901363
  6. Bel, E. H. (2013) Clinical practice. Mild asthma. N. Engl. J. Med. 369, 549-557.  https://doi.org/10.1056/NEJMcp1214826
  7. Bergsbaken, T., Fink, S. L. and Cookson, B. T. (2009) Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 7, 99-109.  https://doi.org/10.1038/nrmicro2070
  8. Besnard, A. G., Guillou, N., Tschopp, J., Erard, F., Couillin, I., Iwakura, Y., Quesniaux, V., Ryffel, B. and Togbe, D. (2011) NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy 66, 1047-1057.  https://doi.org/10.1111/j.1398-9995.2011.02586.x
  9. Bivik, C., Verma, D., Winge, M. C., Lieden, A., Bradley, M., Rosdahl, I. and Soderkvist, P. (2013) Genetic variation in the inflammasome and atopic dermatitis susceptibility. J. Invest. Dermatol. 133, 2486-2489.  https://doi.org/10.1038/jid.2013.168
  10. Boguniewicz, M. and Leung, D. Y. (2010) Recent insights into atopic dermatitis and implications for management of infectious complications. J. Allergy Clin. Immunol. 125, 4-13.  https://doi.org/10.1016/j.jaci.2009.11.027
  11. Brandt, E. B. and Sivaprasad, U. (2011) Th2 cytokines and atopic dermatitis. J. Clin. Cell. Immunol. 2, 110. 
  12. Chanez, P. (2005) Severe asthma is an epithelial disease. Eur. Respir. J. 25, 945-946.  https://doi.org/10.1183/09031936.05.00038605
  13. Coll, R. C., Robertson, A., Butler, M., Cooper, M. and O'Neill, L. A. (2011) The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes. PLoS One 6, e29539. 
  14. Colomar, A., Marty, V., Medina, C., Combe, C., Parnet, P. and Amedee, T. (2003) Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse Schwann cells require the stimulation of P2X7 receptors. J. Biol. Chem. 278, 30732-30740.  https://doi.org/10.1074/jbc.M304534200
  15. Davies, D. E. (2009) The role of the epithelium in airway remodeling in asthma. Proc. Am. Thorac. Soc. 6, 678-682.  https://doi.org/10.1513/pats.200907-067DP
  16. Denes, A., Lopez-Castejon, G. and Brough, D. (2012) Caspase-1: is IL-1 just the tip of the ICEberg? Cell Death Dis. 3, e338. 
  17. dos Santos, C. C. (2012) The role of the inflammasome in ventilator-induced lung injury. Am. J. Respir. Crit. Care Med. 185, 1141-1144.  https://doi.org/10.1164/rccm.201204-0649ED
  18. Fu, Y., Wang,Y., Du, L., Xu, C., Cao, J., Fan, T., Liu, J., Su, X., Fan, S., Liu, Q. and Fan, F. (2013) Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation. Int. J. Mol. Sci. 14, 14105-14118.  https://doi.org/10.3390/ijms140714105
  19. Gross, O., Thomas, C. J, Guarda, G. and Tschopp, J. (2011) The inflammasome: an integrated view. Immunol. Rev. 243, 136-151.  https://doi.org/10.1111/j.1600-065X.2011.01046.x
  20. Hoffman, H. M., Mueller, J. L., Broide, D. H., Wanderer, A. A. and Kolodner, R. D. (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet. 29, 301-305.  https://doi.org/10.1038/ng756
  21. Holgate, S. T., Roberts, G., Arshad, H. S., Howarth, P. H. and Davies, D. E. (2009) The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis. Proc. Am. Thorac. Soc. 6, 655-659.  https://doi.org/10.1513/pats.200907-072DP
  22. Holgate, S. T. (2000) Epithelial damage and response. Clin. Exp. Allergy 30 Suppl 1, 37-41.  https://doi.org/10.1046/j.1365-2222.2000.00095.x
  23. Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A. and Latz, E. (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847-856.  https://doi.org/10.1038/ni.1631
  24. Huang, Y., Jiang, H., Chen, Y., Wang, X., Yang, Y., Tao, J., Deng, X., Liang, G., Zhang, H., Jiang, W. and Zhou, R. (2018) Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol. Med. 10, e8689. 
  25. Jang, H. Y., Koo, J. H., Lee, S. M. and Park, B. H. (2018) Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes. Exp. Mol. Med. 50, 1-9.  https://doi.org/10.1038/s12276-018-0104-3
  26. Jiao, D., Wong, C. K., Qiu, H. N., Dong, J., Cai, Z., Chu, M., Hon, K. L., Tsang, M. S. and Lam, C. W. (2016) NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation. Cell. Mol. Immunol. 13, 535-550.  https://doi.org/10.1038/cmi.2015.77
  27. Kabashima, K. (2013) New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J. Dermatol. Sci. 70, 3-11.  https://doi.org/10.1016/j.jdermsci.2013.02.001
  28. Kamo, N., Ke, B., Ghaffari, A. A., Shen, X. D., Busuttil, R. W., Cheng, G. and Kupiec-Weglinski, J. W. (2013) ASC/caspase-1/IL-1β signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia/reperfusion injury. Hepatology 58, 351-362.  https://doi.org/10.1002/hep.26320
  29. Kanneganti, T. D., Ozoren, N., Body-Malapel, M., Amer, A., Park, J. H., Franchi, L., Whitfield, J., Barchet, W., Colonna, M., Vandenabeele, P., Bertin, J., Coyle, A., Grant, E. P., Akira, S. and Nunez, G. (2006) Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440, 233-236.  https://doi.org/10.1038/nature04517
  30. Kayagaki, N., Stowe, I. B., Lee, B. L., O'Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., Liu, P. S., Lill, J. R., Li, H., Wu, J., Kummerfeld, S., Zhang, J., Lee, W. P., Snipas, S. J., Salvesen, G. S., Morris, L. X., Fitzgerald, L., Zhang, Y., Bertram, E. M., Goodnow, C. C. and Dixit, V. M. (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666-671.  https://doi.org/10.1038/nature15541
  31. Kesavardhana, S. and Kanneganti, T. D. (2017) Mechanisms governing inflammasome activation, assembly and pyroptosis induction. Int. Immunol. 29, 201-210. https://doi.org/10.1093/intimm/dxx018
  32. Lambrecht, B. N. and Hammad, H. (2003) Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat. Rev. Immunol. 3, 994-1003.  https://doi.org/10.1038/nri1249
  33. Lambrecht, B. N. and Hammad, H. (2012) The airway epithelium in asthma. Nat. Med. 18, 684-692.  https://doi.org/10.1038/nm.2737
  34. Land, W. G. (2013) Transfusion-related acute lung injury: the work of DAMPs. Transfus. Med. Hemother. 40, 3-13.  https://doi.org/10.1159/000345688
  35. Liang, Y., Chang, C. and Lu, Q. (2016) The genetics and epigenetics of atopic dermatitis-filaggrin and other polymorphisms. Clin. Rev. Allergy Immunol. 51, 315-328.  https://doi.org/10.1007/s12016-015-8508-5
  36. Liu, W., Guo, W., Wu, J., Luo, Q., Tao, F., Gu, Y., Shen, Y., Li, J., Tan, R., Xu, Q. and Sun, Y. (2013) A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem. Pharmacol. 85, 1504-1512.  https://doi.org/10.1016/j.bcp.2013.03.008
  37. Luo, Y. P., Jiang, L., Kang, K., Fei, D. S., Meng, X. L., Nan, C. C., Pan, S. H., Zhao, M. R. and Zhao, M. Y. (2014) Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1. Int. Immunopharmacol. 20, 24-32.  https://doi.org/10.1016/j.intimp.2014.02.017
  38. Macaluso, F., Nothnagel, M., Parwez, Q., Petrasch-Parwez, E., Bechara, F. G., Epplen, J. T. and Hoffjan, S. (2007) Polymorphisms in NACHT-LRR (NLR) genes in atopic dermatitis. Exp. Dermatol. 16, 692-698.  https://doi.org/10.1111/j.1600-0625.2007.00589.x
  39. Man, S. M. and Kanneganti, T. D. (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol. 16, 7-21.  https://doi.org/10.1038/nri.2015.7
  40. Mariathasan, S. and Monack, D. M. (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat. Rev. Immunol. 7, 31-40.  https://doi.org/10.1038/nri1997
  41. Mariathasan, S., Newton, K., Monack, D. M., Vucic, D., French. D. M., Lee, W. P., Roose-Girma, M., Erickson, S. and Dixit, V. M. (2004) Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430, 213-218.  https://doi.org/10.1038/nature02664
  42. Marples, R. R., Heaton, C. L. and Kligman, A. M. (1973) Staphylococcus aureus in psoriasis. Arch. Dermatol. 107, 568-570.  https://doi.org/10.1001/archderm.1973.01620190044010
  43. Martin, G. S., Mannino, D. M., Eaton, S. and Moss, M. (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med. 348, 1546-1554.  https://doi.org/10.1056/NEJMoa022139
  44. Martinez-Giron, R. and van Woerden, H. C. (2010) Disruption of airway epithelium in asthma pathogenesis: are protozoa responsible? Proc. Am. Thorac. Soc. 7, 161. 
  45. Martinon, F., Burns, K. and Tschopp, J. (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10, 417-426.  https://doi.org/10.1016/S1097-2765(02)00599-3
  46. Masters, S. L., Simon, A., Aksentijevich, I. and Kastner, D. L. (2009) Horror autoinflammaticus: the molecular pathophysiology of auto-inflammatory disease (*). Annu. Rev. Immunol. 27, 621-668.  https://doi.org/10.1146/annurev.immunol.25.022106.141627
  47. Munoz-Planillo, R., Franchi, L., Miller, L. S. and Nunez, G. (2009) A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J. Immunol. 183, 3942-3948.  https://doi.org/10.4049/jimmunol.0900729
  48. Nathan, C. (2002) Points of control in infl ammation. Nature 420, 846-852  https://doi.org/10.1038/nature01320
  49. Niebuhr, M., Baumert, K., Heratizadeh, A., Satzer, I. and Werfel, T. (2014) Imparied NLRP3 inflammasome expression and function in atopic dermatitis due to Th2 milieu. Allergy 69, 1058-1067.  https://doi.org/10.1111/all.12428
  50. Perregaux, D. and Gabel, C. A. (1994) Interleukin-1 beta 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. 269, 15195-15203.  https://doi.org/10.1016/S0021-9258(17)36591-2
  51. Petrilli, V., Papin, S., Dostert, C., Mayor, A., Martinon, F. and Tschopp, J. (2007) Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14, 1583-1589.  https://doi.org/10.1038/sj.cdd.4402195
  52. Rankin, J. A. (2004) Biological mediators of acute inflammation. AACN Clin. Issues 15, 3-17.  https://doi.org/10.1097/00044067-200401000-00002
  53. Shi, J., Zhao, Y., Wang, K., Shi, X., Wang, Y., Huang, H., Zhuang, Y., Cai, T., Wang, F. and Shao, F. (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660-665.  https://doi.org/10.1038/nature15514
  54. Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., Rentsendorj, A., Vargas, M., Guerrero, C., Wang, Y., Fitzgerald, K. A., Underhill, D. M., Town, T. and Arditi, M. (2012) Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36, 401-414.  https://doi.org/10.1016/j.immuni.2012.01.009
  55. Soumelis, V., Reche, P. A., Kanzler, H., Yuan, W., Edward, G., Homey, B., Gilliet, M., Ho, S., Antonenko, S., Lauerma, A., Smith, K., Gorman, D., Zurawski, S., Abrams, J., Menon, S., McClanahan, T., de Waal-Malefyt Rd, R., Bazan, F., Kastelein, R. A. and Liu, Y. J. (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673-680.  https://doi.org/10.1038/ni805
  56. Tanaka, H., Miyazaki, N., Oashi, K., Teramoto, S., Shiratori, M., Hashimoto, M., Ohmichi, M. and Abe, S. (2001) IL-18 might reflect disease activity in mild and moderate asthma exacerbation. J. Allergy Clin. Immunol. 107, 331-336.  https://doi.org/10.1067/mai.2001.112275
  57. Tsai, T., Chiang, K., Hung, J., Chang, W., Lin, H., Shien, J., Chong, I. and Hsu, Y. (2018) Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome. Int. J. Mol. Med. 41, 757-764.  https://doi.org/10.3892/ijmm.2017.3310
  58. Tomi, N. S., Kranke, B. and Aberer, E. (2005) Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and erythroderma, and in healthy control subjects. J. Am. Acad. Dermatol. 53, 67-72.  https://doi.org/10.1016/j.jaad.2005.02.034
  59. van de Veerdonk, F. L., Netea, M. G., Dinarello, C. A. and Joosten, L. A. (2011) Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 32, 110-116.  https://doi.org/10.1016/j.it.2011.01.003
  60. Weidinger, S. and Novak, N. (2016) Atopic dermatitis. Lancet 387, 1109-1122.  https://doi.org/10.1016/S0140-6736(15)00149-X
  61. Whelan, R., Kim, C., Chen, M., Leiter, J., Grunstein, M. M. and Hakonarson, H. (2004) Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle. Eur. Respir. J. 24, 559-567.  https://doi.org/10.1183/09031936.04.00133803
  62. Willingham, S. B., Allen, I. C., Bergstralh, D. T., Brickey, W. J., Huang, M. T., Taxman, D. J., Duncan, J. A. and Ting, J. P. (2009) NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J. Immunol. 183, 2008-2015.  https://doi.org/10.4049/jimmunol.0900138
  63. Wilson, K. P., Black, J. A., Thomson, J. A., Kim, E. E., Griffith, J. P., Navia, M. A., Murcko, M. A., Chambers, S. P., Aldape, R. A., Raybuck, S. A. and Livingston, D. J. (1994) Structure and mechanism of interleukin-1 beta converting enzyme. Nature 370, 270-275.  https://doi.org/10.1038/370270a0
  64. Yeretssian, G., Labbe, K. and Saleh, M. (2008) Molecular regulation of inflammation and cell death. Cytokine 43, 380-390.  https://doi.org/10.1016/j.cyto.2008.07.015
  65. Yin, H., Li, X., Yuan, B., Zhang, B., Hu, S., Gu, H., Jin, X. and Zhu, J. (2011) Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33. Int. Immunopharmacol. 11, 2112-2117.  https://doi.org/10.1016/j.intimp.2011.09.004
  66. Zhang, Q., Fan, H. W., Zhang, J. Z., Wang, Y. M. and Xing, H. J. (2015) NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans. Genet. Mol. Res. 14, 13968-13980.  https://doi.org/10.4238/2015.October.29.17
  67. Zhou, R., Tardivel, A., Thorens, B., Choi, I. and Tschopp, J. (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 11, 136-140.  https://doi.org/10.1038/ni.1831