Advertisement

Inflammasomes in Clinical Practice: A Brief Introduction

  • Elísabet Alcocer-Gómez
  • Beatriz Castejón-Vega
  • Macarena López-Sánchez
  • Mario D. Cordero
Chapter
Part of the Experientia Supplementum book series (EXS, volume 108)

Abstract

Inflammasomes are multiprotein complexes formed and activated after exposure to pathogenic microbes and host danger signals that control the maturation and production of IL-1β and IL-18. Their implication in different diseases such as cardiovascular, neurodegenerative, psychiatric, and metabolic diseases opens a door to developing new therapeutic perspectives. However, the rapid increase in the knowledge about inflammasomes is associated with their involvement in clinical practice. Two topics open the way to future lines of research: a clinical trial with the new specific inhibitors and the development of diagnostic tools.

Keywords

Inflammasomes NLRP3 Clinical medicine Diagnosis Pharmacological treatment 

References

  1. Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M (2015) NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 4:296–307CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ajdukovic J (2015) The role of NLRP3 inflammasome in cardiovascular diseases. J Clin Exp Cardiol 6:399Google Scholar
  3. Alcocer-Gómez E, Cordero MD (2017) NLRP3 inflammasome: common nexus between depression and cardiovascular diseases. Nat Rev Cardiol 14:124CrossRefPubMedGoogle Scholar
  4. Alcocer-Gómez E, de Miguel M, Casas-Barquero N, Núñez-Vasco J, Sánchez-Alcazar JA, Fernández-Rodríguez A, Cordero MD (2013) NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav Immun 36:111–117CrossRefGoogle Scholar
  5. Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, Barberà-Cremades M, Yagüe J, Ruiz-Ortiz E, Antón J, Buján S, Couillin I, Brough D, Arostegui JI, Pelegrín P (2014) The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 15:738–748CrossRefPubMedGoogle Scholar
  6. Braga TT, Forni MF, Correa-Costa M, Ramos RN, Barbuto JA, Branco P, Castoldi A, Hiyane MI, Davanso MR, Latz E, Franklin BS, Kowaltowski AJ, Camara NO (2017) Soluble uric acid activates the NLRP3 inflammasome. Sci Rep 7:39884CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bullón P, Cano-García FJ, Alcocer-Gómez E, Varela-López A, Roman-Malo L, Ruiz-Salmerón RJ, Quiles JL, Navarro-Pando JM, Battino M, Ruiz-Cabello J, Jiménez-Borreguero LJ, Cordero MD (2017) Could NLRP3-inflammasome be a cardiovascular risk biomarkers in acute myocardial infarction patients? Antioxid Redox Signal 27:269–275CrossRefPubMedGoogle Scholar
  8. Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med 21:248–255CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cordero MD, Williams MR, Ryffel B (2018) AMP-activated protein kinase regulation of the NLRP3 inflammasome during aging. Trends Endocrinol Metab 29:8–17CrossRefPubMedGoogle Scholar
  10. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–1361CrossRefPubMedPubMedCentralGoogle Scholar
  11. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934CrossRefPubMedPubMedCentralGoogle Scholar
  12. Grinstein L, Endter K, Hedrich CM, Reinke S, Luksch H, Schulze F, Robertson AAB, Cooper MA, Rösen-Wolff A, Winkler S (2017) An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes. Clin Immunol. pii: S1521-6616(17)30179-1Google Scholar
  13. Hafner-Bratkovic I, Bencina M, Fitzgerald KA, Golenbock D, Jerala R (2012) NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1beta and neuronal toxicity. Cell Mol Life Sci 69:4215–4228CrossRefPubMedPubMedCentralGoogle Scholar
  14. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT (2013) NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678CrossRefPubMedGoogle Scholar
  15. Heneka MT, Kummer MP, Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14:463–477CrossRefPubMedGoogle Scholar
  16. Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasomes. Cell 157:1013–1022CrossRefPubMedGoogle Scholar
  17. Martín-Sánchez F, Compan V, Pelegrín P (2016) Measuring NLR oligomerization III: detection of NLRP3 complex by bioluminescence resonance energy transfer. Methods Mol Biol 1417:159–168CrossRefPubMedGoogle Scholar
  18. Masters CL, Selkoe DJ (2012) Biochemistry of amyloid 𝛽-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006262CrossRefPubMedPubMedCentralGoogle Scholar
  19. Sadatomi D, Nakashioya K, Mamiya S, Honda S, Kameyama Y, Yamamura Y, Tanimura S, Takeda K (2017) Mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation. J Biochem 161:503–512PubMedGoogle Scholar
  20. Yang CA, Chiang BL (2015) Inflammasomes and human autoimmunity: a comprehensive review. J Autoimmun 61:1–8CrossRefPubMedGoogle Scholar
  21. Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D’Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD (2015) The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 21:263–269CrossRefPubMedPubMedCentralGoogle Scholar
  22. Zhou Y, Lu M, Du RH, Qiao C, Jiang CY, Zhang KZ, Ding JH, Hu G (2016) MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease. Mol Neurodegener 11:28CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Elísabet Alcocer-Gómez
    • 1
  • Beatriz Castejón-Vega
    • 2
    • 3
  • Macarena López-Sánchez
    • 3
    • 4
  • Mario D. Cordero
    • 4
    • 5
  1. 1.Departamento de Psicología ExperimentalFacultad de Psicología, Universidad de SevillaSevillaSpain
  2. 2.Departamento de Psicología ExperimentalFacultad de Psicología, University of SevillaSevillaSpain
  3. 3.Research Laboratory, Oral Medicine DepartmentUniversity of SevillaSevillaSpain
  4. 4.Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de AndalucíaSevillaSpain
  5. 5.Department of Physiology, Institute of Nutrition and Food Technology “José Mataix”, Biomedical Research Center (CIBM)University of GranadaArmillaSpain

Personalised recommendations