The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

被引:2419
作者
Kelley, Nathan [1 ]
Jeltema, Devon [1 ]
Duan, Yanhui [1 ]
He, Yuan [1 ]
机构
[1] Wayne State Univ, Sch Med, Dept Biochem Microbiol & Immunol, Detroit, MI 48201 USA
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 13期
关键词
NLRP3; inflammasome; Priming; Ionic flux; ROS; Mitochondrial dysfunction; Lysosomal damage; Post-translational modification; regulators; NALP3; INFLAMMASOME; K+ EFFLUX; PATTERN-RECOGNITION; AIM2; OXIDATIVE STRESS; DENDRITIC CELLS; PORE FORMATION; BACTERIAL RNA; P2X7; RECEPTOR; GASDERMIN D;
D O I
10.3390/ijms20133328
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1 beta/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer's disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
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页数:24
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共 171 条
  • [1] Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming
    Allam, Ramanjaneyulu
    Lawlor, Kate E.
    Yu, Eric Chi-Wang
    Mildenhall, Alison L.
    Moujalled, Donia M.
    Lewis, Rowena S.
    Ke, Francine
    Mason, Kylie D.
    White, Michael J.
    Stacey, Katryn J.
    Strasser, Andreas
    O'Reilly, Lorraine A.
    Alexander, Warren
    Kile, Benjamin T.
    Vaux, David L.
    Vince, James E.
    [J]. EMBO REPORTS, 2014, 15 (09) : 982 - 990
  • [2] The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA
    Allen, Irving C.
    Scull, Margaret A.
    Moore, Chris B.
    Holl, Eda K.
    McElvania-TeKippe, Erin
    Taxman, Debra J.
    Guthrie, Elizabeth H.
    Pickles, Raymond J.
    Ting, Jenny P. -Y.
    [J]. IMMUNITY, 2009, 30 (04) : 556 - 565
  • [3] The P2X7 receptor: Shifting from a low- to a high-conductance channel - An enigmatic phenomenon?
    Alves, Luiz Anastacio
    de Melo Reis, Ricardo Augusto
    Magalhaes de Souza, Cristina Alves
    de Freitas, Monica Santos
    Nogueira Teixeira, Pedro Celso
    Moreira Ferreira, Dinarte Neto
    Xavier, Robson Faria
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2014, 1838 (10): : 2578 - 2587
  • [4] NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5
    Baker, Paul J.
    Boucher, Dave
    Bierschenk, Damien
    Tebartz, Christina
    Whitney, Paul G.
    D'Silva, Damian B.
    Tanzer, Maria C.
    Monteleone, Mercedes
    Robertson, Avril A. B.
    Cooper, Matthew A.
    Alvarez-Diaz, Silvia
    Herold, Marco J.
    Bedoui, Sammy
    Schroder, Kate
    Masters, Seth L.
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2015, 45 (10) : 2918 - 2926
  • [5] Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa
    Balakrishnan, Arjun
    Karki, Rajendra
    Berwin, Brent
    Yamamoto, Masahiro
    Kanneganti, Thirumala-Devi
    [J]. CELL DEATH DISCOVERY, 2018, 4
  • [6] Boron-Based Inhibitors of the NLRP3 Inflammasome
    Baldwin, Alex G.
    Rivers-Auty, Jack
    Daniels, Michael J. D.
    White, Claire S.
    Schwalbe, Carl H.
    Schilling, Tom
    Hammadi, Halah
    Jaiyong, Panichakorn
    Spencer, Nicholas G.
    England, Hazel
    Luheshi, Nadia M.
    Kadirvel, Manikandan
    Lawrence, Catherine B.
    Rothwell, Nancy J.
    Harte, Michael K.
    Bryce, Richard A.
    Allan, Stuart M.
    Eder, Claudia
    Freeman, Sally
    Brough, David
    [J]. CELL CHEMICAL BIOLOGY, 2017, 24 (11) : 1321 - +
  • [7] Adenovirus Membrane Penetration Activates the NLRP3 Inflammasome
    Barlan, A. U.
    Griffin, T. M.
    Mcguire, K. A.
    Wiethoff, C. M.
    [J]. JOURNAL OF VIROLOGY, 2011, 85 (01) : 146 - 155
  • [8] SUMO-mediated regulation of NLRP3 modulates inflammasome activity
    Barry, Rachael
    John, Sidonie Wicky
    Liccardi, Gianmaria
    Tenev, Tencho
    Jaco, Isabel
    Chen, Chih-Hong
    Choi, Justin
    Kasperkiewicz, Paulina
    Fernandes-Alnemri, Teresa
    Alnemri, Emad
    Drag, Marcin
    Chen, Yuan
    Meier, Pascal
    [J]. NATURE COMMUNICATIONS, 2018, 9
  • [9] Cutting Edge: Reactive Oxygen Species Inhibitors Block Priming, but Not Activation, of the NLRP3 Inflammasome
    Bauernfeind, Franz
    Bartok, Eva
    Rieger, Anna
    Franchi, Luigi
    Nunez, Gabriel
    Hornung, Veit
    [J]. JOURNAL OF IMMUNOLOGY, 2011, 187 (02) : 613 - 617
  • [10] Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression
    Bauernfeind, Franz G.
    Horvath, Gabor
    Stutz, Andrea
    Alnemri, Emad S.
    MacDonald, Kelly
    Speert, David
    Fernandes-Alnemri, Teresa
    Wu, Jianghong
    Monks, Brian G.
    Fitzgerald, Katherine A.
    Hornung, Veit
    Latz, Eicke
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 183 (02) : 787 - 791