The NLRP3 inflammasome: molecular activation and regulation to therapeutics

被引：4351

作者：

Swanson, Karen V. ^{[1
]}

Deng, Meng ^{[2
,3
]}

Ting, Jenny P. -Y. ^{[3
,4
,5
,6
]}

机构：

[1] Univ N Carolina, Infect Dis, Dept Med, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Oral & Craniofacial Biomed Program, Sch Dent, Chapel Hill, NC 27515 USA

[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[4] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[5] Univ N Carolina, Inst Inflammatory Dis, Chapel Hill, NC 27515 USA

[6] Univ N Carolina, Ctr Translat Immunol, Chapel Hill, NC 27515 USA

来源：

NATURE REVIEWS IMMUNOLOGY | 2019年 / 19卷 / 08期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; CUTTING EDGE; GASDERMIN-D; NALP3; INFLAMMASOME; K+ EFFLUX; AIM2; CELL-DEATH; INTERLEUKIN-1-BETA MATURATION; DIFFERENTIAL REQUIREMENT; HUMAN MONOCYTES;

D O I：

10.1038/s41577-019-0165-0

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1 beta and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical bases of NLRP3 activation and regulation and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.

引用

页码：477 / 489

页数：13

共 179 条

[1]

Caspase-11 Protects Against Bacteria That Escape the Vacuole [J].

Aachoui, Youssef ;

Leaf, Irina A. ;

Hagar, Jon A. ;

Fontana, Mary F. ;

Campos, Cristine G. ;

Zak, Daniel E. ;

Tan, Michael H. ;

Cotter, Peggy A. ;

Vance, Russell E. ;

Aderem, Alan ;

Miao, Edward A. .

SCIENCE, 2013, 339 (6122) :975-978

[2]

Cyclic-di-GMP and cyclic-di-AMP activate the NLRP3 inflammasome [J].

Abdul-Sater, Ali A. ;

Tattoli, Ivan ;

Jin, Lei ;

Grajkowski, Andrzej ;

Levi, Assaf ;

Koller, Beverly H. ;

Allen, Irving C. ;

Beaucage, Serge L. ;

Fitzgerald, Katherine A. ;

Ting, Jenny P. -Y. ;

Cambier, John C. ;

Girardin, Stephen E. ;

Schindler, Christian .

EMBO REPORTS, 2013, 14 (10) :900-906

[3]

Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis [J].

Aganna, E ;

Martinon, F ;

Hawkins, PN ;

Ross, JB ;

Swan, DC ;

Booth, DR ;

Lachmann, HJ ;

Gaudet, R ;

Woo, P ;

Feighery, C ;

Cotter, FE ;

Thome, M ;

Hitman, GA ;

Tschopp, J ;

McDermott, MF .

ARTHRITIS AND RHEUMATISM, 2002, 46 (09) :2445-2452

[4]

NALP3 forms an IL-lβ-Processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J].

Agostini, L ;

Martinon, F ;

Burns, K ;

McDermott, MF ;

Hawkins, PN ;

Tschopp, J .

IMMUNITY, 2004, 20 (03) :319-325

[5]

De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID) -: A new member of the expanding family of pyrin-associated autoinflammatory diseases [J].

Aksentijevich, I ;

Nowak, M ;

Mallah, M ;

Chae, JJ ;

Watford, WT ;

Hofmann, SR ;

Stein, L ;

Russo, R ;

Goldsmith, D ;

Dent, P ;

Rosenberg, HF ;

Austin, F ;

Remmers, EF ;

Balow, JE ;

Rosenzweig, S ;

Komarow, H ;

Shoham, NG ;

Wood, G ;

Jones, J ;

Mangra, N ;

Carrero, H ;

Adams, BS ;

Moore, TL ;

Schikler, K ;

Hoffman, H ;

Lovell, DJ ;

Lipnick, R ;

Barron, K ;

O'Shea, JJ ;

Kastner, DL ;

Goldbach-Mansky, R .

ARTHRITIS AND RHEUMATISM, 2002, 46 (12) :3340-3348

[6]

Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming [J].

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. .

EMBO REPORTS, 2014, 15 (09) :982-990

[7]

Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling [J].

Antonopoulos, Christina ;

Russo, Hana M. ;

El Sanadi, Caroline ;

Martin, Bradley N. ;

Li, Xiaoxia ;

Kaiser, William J. ;

Mocarski, Edward S. ;

Dubyak, George R. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (33) :20167-20184

[8]

Proapoptotic Chemotherapeutic Drugs Induce Noncanonical Processing and Release of IL-1β via Caspase-8 in Dendritic Cells [J].

Antonopoulos, Christina ;

El Sanadi, Caroline ;

Kaiser, William J. ;

Mocarski, Edward S. ;

Dubyak, George R. .

JOURNAL OF IMMUNOLOGY, 2013, 191 (09) :4789-4803

[9]

C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation [J].

Asgari, Elham ;

Le Friec, Gaelle ;

Yamamoto, Hidekazu ;

Perucha, Esperanza ;

Sacks, Steven S. ;

Koehl, Joerg ;

Cook, H. Terence ;

Kemper, Claudia .

BLOOD, 2013, 122 (20) :3473-3481

[10]

Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors [J].

Babelova, Andrea ;

Moreth, Kristin ;

Tsalastra-Greul, Wasiliki ;

Zeng-Brouwers, Jinyang ;

Eickelberg, Oliver ;

Young, Marian F. ;

Bruckner, Peter ;

Pfeilschifter, Josef ;

Schaefer, Roland M. ;

Groene, Hermann-Josef ;

Schaefer, Liliana .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (36) :24035-24048

← 1 2 3 4 5 6 7 8 9 10 →