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Colegio de Medicina Interna de México.

2025, Number 08

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Med Int Mex 2025; 41 (08)

NLRP3 inflammasome in health and disease

Rodríguez OAR, Ocegueda GS, Galán CJC, Barrientos RBG, Montelongo OJL, García PME

Language: Spanish
References: 61
Page: 498-511
PDF size: 280.41 Kb.


ABSTRACT

Objective: To update the state of knowledge on the NLRP3 inflammasome, its activation and regulation, and related diseases.
Methodology: A review of the PubMed and Google Scholar databases was conducted to identify clinical trials and review articles published from February 2021 to February 2024 that followed the PRISMA methodology.
Results: The NLRP3 inflammasome remains in a self-suppressed and inactive state. To activate, it requires a second signal, which can originate from pathogens or stressassociated danger pathways. The activation of the NLRP3 inflammasome is linked to several types of cell death. In these types of cell death, an imbalance in signaling mediated by reactive oxygen species and changes in potassium flow play a key role, resulting in a failure to respond to oxidative stress. The NLRP3 inflammasome is maintained in an inactive state and requires a second signal to activate. This signal may come from pathogens or stress-associated danger pathways. The activation or inhibition of NLRP3 is involved in regulating the inflammatory process that amplifies cell damage.
Conclusion: Uncontrolled activation or inhibition of NLRP3 could lead to dysregulation of the inflammatory process that amplifies cell damage in diseases associated with chronic inflammation.


REFERENCES

  1. Bottasso O. La inflamación en el siglo XXI, desde los conceptosclásicos a una visión más extendida. Pinelatam 2022; 2 (2): 116-24. https://revistas.unc.edu.ar/index.php/pinelatam/article/view/38192

  2. Aquino-Domínguez AS, Romero-Tlalolini MA, Aguilar-RuizSR. Los receptores del sistema inmunitario innato. https://uabjo.slm.cloud/?a=article.main&d=true&tf=article&id=WPbIfIQBxoz2Skqwc6DB

  3. Rehwinkel J, Gack MU. RIG-I-like receptors: their regulationand roles in RNA sensing. In Nature Reviews Immunology2020; 20 (9): 537-51). https://doi.org/10.1038/s41577-020-0288-3

  4. Sanz JM, Gómez Lahoz AM, Martín RO. Papel del sistemainmune en la infección por el SARS-CoV-2: inmunopatologíade la COVID-19. Medicine 2021; 13 (33): 1917-31. http://dx.doi.org/10.1016/j.med.2021.05.005

  5. Koncz G, Jenei V, Tóth M, Váradi E, Kardos B, Bácsi A, etal. Damage-mediated macrophage polarization in sterileinflammation. Frent Immunol 2023;14. http://dx.doi.org/10.3389/fimmu.2023.1169560

  6. Mnich ME, van Dalen R, van Sorge NM. C-Type lectin receptorsin host defense against bacterial pathogens. FronCell Infect Microbiol 2020; 10. http://dx.doi.org/10.3389/fcimb.2020.00309

  7. González HV. Enfermedades autoinflamatorias sistémicas,entidades en auge: generalidades, principales síndromesmonogénicos y aproximación al manejo terapéutico.Galicia Clin 2023; 84 (1): 26. https://galiciaclinica.info/PDF/68/4046.pdf

  8. Montaño-Estrada LP, Fortoul Van der Goes TI, Rendón-Huerta EP. ¿Qué son los inflamosomas? El NLRP3 como,por ejemplo. Rev Fac Med (Méx) 2017; 60 ( 1 ): 42-49.

  9. Khurrum S, Sameen F, Hamzah K, Ahmed E, et al. PodocytespecificNlrp3 inflammasome activation promotes diabetic kidney disease. Kidney Interna 2022; 102 (4): 766-79.https://doi.org/10.1016/j.kint.2022.06.010

  10. Pérez AB. Receptores de reconocimiento de patrones, supapel en la inmunidad innata. Academia Lab 2020. https://www.academia.edu/45171368/receptores_de_reconocimiento_de_patrones_su_papel_en_la_inmunidad_innata

  11. Suárez R, Buelvas N. El inflamasoma: mecanismos deactivación. Invest Clin 2015; 56 (1): 074-099. http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0535-51332015000100009&lng=es

  12. Zhang Z, Venditti R, Ran L, et al. Distinct changes in endosomalcomposition promote NLRP3 inflammasomeactivation. Nat Immunol 2023; 24: 3041. https://doi.org/10.1038/s41590-022-01355-3

  13. Park YJ, Dodantenna N, Kim Y, Kim T, et al. MARCH5‐dependentNLRP3 ubiquitination is required for mitochondrialNLRP3‐NEK7 complex formation and NLRP3 inflammasomeactivation. EMBO J 2023; 42 (19). https://doi.org/10.15252/embj.2023113481

  14. Qianqian Di, Xibao Z, Haimei T, Xunwei L, et al. USP22 suppressesthe NLRP3 inflammasome by degrading NLRP3 viaATG5-dependent autophagy. Autophagy 2023; 19 (3): 873-885. https://doi.org/10.1080/15548627.2022.2107314

  15. Dongsheng B, Jiaying D, Xiumin B, Wangjia C, et al. ALDOAmaintains NLRP3 inflammasome activation by controllingAMPK activation. Autophagy 2022; 18: (7): 1673-93.https://doi.org/10.1080/15548627.2021.1997051

  16. Xu T, Yu W, Fang H, et al. Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation. CellDeath Differ 2022; 29: 1582-95. https://doi.org/10.1038/s41418-022-00947-8

  17. Ohto U, Kamitsukasa Y, Ishida H, Zhang Z, et al. Structuralbasis for the oligomerization-mediated regulation of NLRP3inflammasome activation. PNAS 2022; 119 (11). https://doi.org/10.1073/pnas.2121353119

  18. Zhan X, Li Q, Xu G, Xiao X, et al. The mechanism of NLRP3inflammasome activation and its pharmacological inhibitors.Front Immunol 2023; 13. https://doi.org/10.3389/fimmu.2022.1109938

  19. Zhang T, Zhao J, Liu T, Cheng W, et al. A novel mechanismfor NLRP3 inflammasome activation. Metabolism Open

  20. 2022; 13. https://doi.org/10.1016/j.metop.2022.10016620. Wang L, Ren W, Wu QJ, Liu T, et al. NLRP3 InflammasomeActivation: a therapeutic target for cerebral Ischemia–Reperfusioninjury. Front Mol Neurosci 2022; 15. https://doi.org/10.3389/fnmol.2022.847440

  21. Billingham LK, Stoolman JS, Vasan K, et al. Mitochondrialelectron transport chain is necessary for NLRP3 inflammasomeactivation. Nat Immunol 2022; 23: 692-704. https://doi.org/10.1038/s41590-022-01185-3

  22. Lee KG, Hong BK, Lee S, et al. Nuclear receptor coactivator6 is a critical regulator of NLRP3 inflammasome activationand gouty arthritis. Cell Mol Immunol 2024; 21: 227-44.https://doi.org/10.1038/s41423-023-01121-x

  23. Qiu Y, Huang Y, Chen M, Yang Y, et al. Mitochondrial DNAin NLRP3 inflammasome activation. Int Immunophar 2022;108. https://doi.org/10.1016/j.intimp.2022.108719

  24. Motta V, Soares F, Sun T, Philpott DJ. NOD-like receptors:Versatile cytosolic sentinels. Physiol Rev 2015; 95 (1):149-78. http://dx.doi.org/10.1152/physrev.00009.2014

  25. Gong T, Liu L, Jiang W, Zhou R. DAMP-sensing receptors insterile inflammation and inflammatory diseases. Nat RevImmunol 2020; 20 (2): 95-112. http://dx.doi.org/10.1038/s41577-019-0215-7

  26. De Carvalho RM, Szabo G. Role of the inflammasome inliver disease. Annu Rev Pathol 2022; 17 (1): 345-65. http://dx.doi.org/10.1146/annurev- pathmechdis-032521-102529

  27. Negash AA, Olson RM, Griffin S, Gale M. Modulation ofcalcium signaling pathway by hepatitis C virus core proteinstimulates NLRP3 inflammasome activation. PLoS Pathog2019; 15 (2): e1007593. http://dx.doi.org/10.1371/journal.ppat.1007593

  28. Martínez-Cardona C. Role of the AIM2 inflammasome inthe development of hepatocellular carcinoma. Rua 2019.http://hdl.handle.net/10045/90991

  29. Ding X, Lei Q, Li T, Li L, et al. Hepatitis B core antigencan regulate NLRP3 inflammasome pathway in HepG2cells. J Medical Virol 2019; 91 (8): 1528-36. https://doi.org/10.1002/jmv.25490

  30. Dinarello CA. Overview of the IL‐1 family in innate inflammationand acquired immunity. Immunol Rev 2018; 281(1): 8-27. http://dx.doi.org/10.1111/imr.12621

  31. Tsutsui H, Cai X, Hayashi S. Interleukin-1 family cytokinesin liver diseases. Mediators Inflamm. 2015; 2015: 1-19.http://dx.doi.org/10.1155/2015/630265

  32. Karki R, Man SM, Kanneganti T-D. Inflammasomes andcancer. Cancer Immunol Res 2017; 5 (2): 94-9. https://dx.doi.org/10.1158/2326-6066.cir-16-0269

  33. Moossavi M, Parsamanesh N, Bahrami A, Atkin SL, SahebkarA. Role of the NLRP3 inflammasome in cancer. Mol Cancer2018; 17 (1). http://dx.doi.org/10.1186/s12943-018-0900-3

  34. Yu C, Chen P, Miao L, Di G. The role of the NLRP3 inflammasomeand programmed cell death in acute liver injury.Int J Mol Sci 2023; 24 (4): 3067. http://dx.doi.org/10.3390/ijms24043067

  35. MOLINA LÓPEZ, María Cristina. Regulation of the NLRP3inflammasome in autoinflammatory diseases and its involvementin metabolism. Research Project 2024.

  36. Karasawa T, Komada T, Yamada N, Aizawa E, Mizushina Y,Watanabe S, et al. Cryo-sensitive aggregation triggers NLRP3inflammasome assembly in cryopyrin-associated periodic syndrome.Elife 2022; 11. https://dx.doi.org/10.7554/elife.75166

  37. Sobradillo Ecenarro P. Role of the Inflammasome in Stableand Exacerbated COPD 2022.

  38. Yang W, Ni H, Wang H, Gu H. NLRP3 inflammasome is essentialfor the development of chronic obstructive pulmonarydisease. Int J Clin Exp Pathol 2015; 8 (10): 13209-16.

  39. Hosseinian N, Cho Y, Lockey RF, Kolliputi N. The roleof the NLRP3 inflammasome in pulmonary diseases.Ther Adv Respir Dis 2015; 9 (4): 188-97. http://dx.doi.org/10.1177/1753465815586335

  40. Cui Y, Yu H, Bu Z, Wen L, Yan L, Feng J. Focus on the roleof the NLRP3 inflammasome in multiple sclerosis: Pathogenesis,diagnosis, and therapeutics. Front Mol Neurosci2022; 15. http://dx.doi.org/10.3389/fnmol.2022.894298

  41. Bai H, Zhang Q. Activation of NLRP3 inflammasome andonset of Alzheimer’s disease. Front Immunol 2021; 12.http://dx.doi.org/10.3389/fimmu.2021.701282

  42. Milner MT, Maddugoda M, Götz J, Burgener SS, SchroderK. The NLRP3 inflammasome triggers sterile neuroinflammationand Alzheimer’s disease. Curr Opin Immunol 2021;68: 116–24. http://dx.doi.org/10.1016/j.coi.2020.10.011

  43. Ruano, L. Role of diet in Parkinson´s disease. 2024. DOI:https://hdl.handle.net/10953.1/21421

  44. Haque ME, Akther M, Jakaria M, Kim I-S, Azam S, Choi D-K.Targeting the microglial NLRP3 inflammasome and its rolein Parkinson’s disease. Mov Disord 2020; 35 (1):20-33.http://dx.doi.org/10.1002/mds.27874

  45. Wang S, Yuan Y-H, Chen N-H, Wang H-B. The mechanismsof NLRP3 inflammasome/pyroptosis activation and theirrole in Parkinson’s disease. Int Immunopharmacol 2019; 67:458-64. http://dx.doi.org/10.1016/j.intimp.2018.12.019

  46. Zhenga X, Zhao D, Jin Y, Liu Y, Liu D. Role of the NLRP3inflammasome in gynecological disease. Biomed Pharmacother2023; 166 (115393): 115393. http://dx.doi.org/10.1016/j.biopha.2023.115393

  47. Zhou F, Zhao F, Huang Q, Lin X, Zhang S, Dai Y. NLRP3activated macrophages promote endometrial stromalcells migration in endometriosis. J Reprod Immunol 2022;152 (103649): 103649. DOI: http://dx.doi.org/10.1016/j.jri.2022.103649

  48. Wang D, Weng Y, Zhang Y, Wang R, Wang T, Zhou J, et al.Exposure to hyperandrogen drives ovarian dysfunction andfibrosis by activating the NLRP3 inflammasome in mice. SciTotal Environ 2020; 745 (141049): 141049. http://dx.doi.org/10.1016/j.scitotenv.2020.141049

  49. Deng R, Zhang H-L, Huang J-H, Cai R-Z, Wang Y, Chen Y-H,et al. MAPK1/3 kinase-dependent ULK1 degradation attenuatesmitophagy and promotes breast cancer bonemetastasis. Autophagy 2021; 17 (10): 3011-29. http://dx.doi.org/10.1080/15548627.2020.1850609

  50. Williams BM, Cliff CL, Lee K, Squires PE, Hills CE. The roleof the NLRP3 inflammasome in mediating glomerular andtubular injury in diabetic nephropathy. Front Physiol 2022;13. http://dx.doi.org/10.3389/fphys.2022.907504

  51. Lachowicz-Scroggins ME, Dunican EM, Charbit AR,Raymond W, Looney MR, Peters MC, et al. ExtracellularDNA, neutrophil extracellular traps, and inflammasomeactivation in severe asthma. Am J Respir Crit Care Med2019; 199 (9): 1076-85. http://dx.doi.org/10.1164/rccm.201810-1869oc

  52. Kim RY, Pinkerton JW, Essilfie AT, Robertson AAB, Baines KJ,Brown AC, et al. Role for NLRP3 inflammasome–mediated,IL-1β–dependent responses in severe, steroid-resistantasthma. Am J Respir Crit Care Med 2017; 196 (3): 283-97.http://dx.doi.org/10.1164/rccm.201609-1830oc

  53. Wu Y, Di X, Zhao M, Li H, et al. The role of the NLRP3 inflammasomein chronic inflammation in asthma and chronicobstructive pulmonary disease. Immun Inflamm Dis 2022;10 (12). http://dx.doi.org/10.1002/iid3.750

  54. Rodríguez-Alcázar JF, Ataide MA, Engels G, Schmitt-Mabmunyo C, et al. Charcot–Leyden crystals activate theNLRP3 inflammasome and cause IL-1β inflammation inhuman macrophages. J Immunol 2019; 202 (2): 550-58.http://dx.doi.org/10.4049/jimmunol.1800107

  55. Olivares Reyes J, Rueda A, Sánchez de la Vega. Nuevas tendenciasde investigación en la señalización celular en la erapost-COVID. CINVESTAV 2023. https://repositorio.cinvestav.mx/bitstream/handle/cinvestav/4866/Nuevas%20tendencias%20de%20investigacion.....pdf?sequence=5#page=72

  56. Sun Qing, Guo Wenxiu, Yue Tun, Wang Luet al. Mecanismosy dianas terapéuticas del inflamasoma NLRP3 en lamiocardiopatía diabética. Gac Méd Méx 2023; 159 ( 3 ):261-67. http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0016-38132023000300261&lng=es

  57. Chan AHP, Moore MJ, Grant AJ, Lam YTM, et al. Selectiveimmunosuppression targeting the NLRP3 inflammasomemitigates the foreign body response to implanted biomaterialswhile preserving angiogenesis. Adv Healthc Mater2023. https://doi.org/10.1002/adhm.202301571

  58. Xia J, Jiang S, Dong S, Liao Y, et al. The role of post-translationalmodifications in regulation of NLRP3 inflammasomeactivation. Int J Mol Sci 2023; 24 (7): 6126. https://www.mdpi.com/1422-0067/24/7/6126

  59. Liu H, Yang X, Liu G. Regulation of cell proliferation andtransdifferentiation compensates for ventilator‐inducedlung injury mediated by NLRP3 inflammasome activation.Immun Inflamm Dis 2023. http://dx.doi.org/10.1002/iid3.1062

  60. Narros P. Nuevas estrategias farmacológicas dirigidas a lainhibición del inflamasoma NLRP3. Universidad Autónomade Madrid 2022. https://repositorio.uam.es/bitstream/handle/10486/703658/narros_fernandez_paloma.pdf?sequence=1&isAllowed=y

  61. Nouel A, Winter JL, Sepúlveda L. Efectos cardiovascularesde los inhibidores del cotransportador 2 de sodio-glucosa(ISGLT2): los mecanismos del beneficio en pacientescon insuficiencia cardíaca. Rev Chil Cardiol 2022; 41 (3):198-205. http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0718-85602022000300198&lng=es




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