Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 5/2010

01-09-2010

Molecular Mechanism of NLRP3 Inflammasome Activation

Authors: Chengcheng Jin, Richard A. Flavell

Published in: Journal of Clinical Immunology | Issue 5/2010

Login to get access

Abstract

The inflammasome is an intracellular multimolecular complex that controls caspase-1 activity in the innate immune system. NLRP3, a member of the NLR family of cytosolic pattern recognition receptors, along with the adaptor protein ASC, mediates caspase-1 activation via assembly of the inflammasome in response to various pathogen-derived factors as well as danger-associated molecules. The active NLRP3 inflammasome drives innate immune response towards invading pathogens and cellular damage, and regulates adaptive immune response. Here, we review identified agonists of the NLRP3 inflammasome and the molecular mechanism by which they induce NLRP3 inflammasome activation. Three signaling pathways involving potassium efflux, generation of reactive oxygen species, and cathepsin B release are discussed.
Literature
1.
Bryant C, Fitzgerald KA. Molecular mechanisms involved in inflammasome activation. Trends Cell Biol. 2009;19(9):455–64.CrossRefPubMed
2.
3.
Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109.CrossRefPubMed
4.
Keller M et al. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132(5):818–31.CrossRefPubMed
5.
Kanneganti TD et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem. 2006;281(48):36560–8.CrossRefPubMed
6.
Muruve DA et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature. 2008;452(7183):103–7.CrossRefPubMed
7.
Wilson D et al. Identifying infection-associated genes of Candida albicans in the postgenomic era. FEMS Yeast Res. 2009;9(5):688–700.CrossRefPubMed
8.
Mariathasan S et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440(7081):228–32.CrossRefPubMed
9.
Kanneganti TD et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature. 2006;440(7081):233–6.CrossRefPubMed
10.
Dostert C et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS ONE. 2009;4(8):e6510.CrossRefPubMed
11.
Gross O et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature. 2009;459(7245):433–6.CrossRefPubMed
12.
Gurcel L et al. Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival. Cell. 2006;126(6):1135–45.CrossRefPubMed
13.
Yamasaki K et al. NLRP3/cryopyrin is necessary for interleukin-1beta (IL-1beta) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J Biol Chem. 2009;284(19):12762–71.CrossRefPubMed
14.
Halle A et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9(8):857–65.CrossRefPubMed
15.
Zhou R et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11(2):136–40.CrossRefPubMed
16.
Martinon F et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.CrossRefPubMed
17.
Dostert C et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320(5876):674–7.CrossRefPubMed
18.
Hornung V et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9(8):847–56.CrossRefPubMed
19.
Cassel SL et al. The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci USA. 2008;105(26):9035–40.CrossRefPubMed
20.
Eisenbarth SC et al. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453(7198):1122–6.CrossRefPubMed
21.
Feldmeyer L et al. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17(13):1140–5.CrossRefPubMed
22.
Watanabe H et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127(8):1956–63.CrossRefPubMed
23.
Sutterwala FS et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 2006;24(3):317–27.CrossRefPubMed
24.
Mayor A et al. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol. 2007;8(5):497–503.CrossRefPubMed
25.
Lamkanfi M, Dixit VM. Inflammasomes: guardians of cytosolic sanctity. Immunol Rev. 2009;227(1):95–105.CrossRefPubMed
26.
Petrilli V et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14(9):1583–9.CrossRefPubMed
27.
Kahlenberg JM, Dubyak GR. Differing caspase-1 activation states in monocyte versus macrophage models of IL-1beta processing and release. J Leukoc Biol. 2004;76(3):676–84.CrossRefPubMed
28.
Perregaux DG, Gabel CA. Human monocyte stimulus-coupled IL-1beta posttranslational processing: modulation via monovalent cations. Am J Physiol. 1998;275(6 Pt 1):C1538–47.PubMed
29.
Perregaux DG, Laliberte RE, Gabel CA. Human monocyte interleukin-1beta posttranslational processing. Evidence of a volume-regulated response. J Biol Chem. 1996;271(47):29830–8.CrossRefPubMed
30.
Cruz CM et al. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem. 2007;282(5):2871–9.CrossRefPubMed
31.
Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47(9):1239–53.CrossRefPubMed
32.
Meissner F, Molawi K, Zychlinsky A. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol. 2008;9(8):866–72.CrossRefPubMed
33.
Fujisawa A et al. Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. Blood. 2007;109(7):2903–11.PubMed
34.
Hentze H et al. Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1-independent necrosis triggered by the microbial toxin nigericin. Cell Death Differ. 2003;10(9):956–68.CrossRefPubMed
35.
Newman ZL, Leppla SH, Moayeri M. CA-074Me protection against anthrax lethal toxin. Infect Immun. 2009;77(10):4327–36.CrossRefPubMed
36.
Metadata
Title
Molecular Mechanism of NLRP3 Inflammasome Activation
Authors
Chengcheng Jin
Richard A. Flavell
Publication date
01-09-2010
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 5/2010
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9440-3

Other articles of this Issue 5/2010

Journal of Clinical Immunology 5/2010 Go to the issue

OriginalPaper

IL-2 Immunotherapy to Recently HIV-1 Infected Adults Maintains the Numbers of IL-17 Expressing CD4+ T (TH17) Cells in the Periphery

OriginalPaper

Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis

OriginalPaper

Characterization of 11 New Cases of Leukocyte Adhesion Deficiency Type 1 with Seven Novel Mutations in the ITGB2 Gene

OriginalPaper

Selective IgA Deficiency in Children in Israel

OriginalPaper

B-Cell and T-Cell Phenotypes in CVID Patients Correlate with the Clinical Phenotype of the Disease

OriginalPaper

The NBS1 Genetic Polymorphisms and the Risk of the Systemic Lupus Erythematosus in Taiwanese Patients
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits