Cutting Edge: NF-kappaB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Jul 3

PMID 19570822

Citations 1425

Authors

Franz G Bauernfeind

Gabor Horvath

Andrea Stutz

Emad S Alnemri

Kelly MacDonald

David Speert

Teresa Fernandes-Alnemri

Jianghong Wu

Brian G Monks

Katherine A Fitzgerald

Veit Hornung

Eicke Latz

Affiliations

Soon will be listed here.

Abstract

The IL-1 family cytokines are regulated on transcriptional and posttranscriptional levels. Pattern recognition and cytokine receptors control pro-IL-1beta transcription whereas inflammasomes regulate the proteolytic processing of pro-IL-1beta. The NLRP3 inflammasome, however, assembles in response to extracellular ATP, pore-forming toxins, or crystals only in the presence of proinflammatory stimuli. How the activation of gene transcription by signaling receptors enables NLRP3 activation remains elusive and controversial. In this study, we show that cell priming through multiple signaling receptors induces NLRP3 expression, which we identified to be a critical checkpoint for NLRP3 activation. Signals provided by NF-kappaB activators are necessary but not sufficient for NLRP3 activation, and a second stimulus such as ATP or crystal-induced damage is required for NLRP3 activation.

Citing Articles

TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways.

Cao R, Zhou J, Liu J, Wang Y, Dai Y, Jiang Y Inflammation. 2025; .

PMID: 40085192 DOI: 10.1007/s10753-025-02282-9.

Vitamin D3 suppresses NLRP3 inflammasome pathway and enhances steroid sensitivity in a neutrophilic steroid hyporesponsive asthma mouse model.

Khalil B, Sharif-Askari N, Selvakumar B, Mdkhana B, Hachim I, Zakri A Inflamm Res. 2025; 74(1):51.

PMID: 40082319 DOI: 10.1007/s00011-025-02009-4.

NLRP3 inflammasome in cardiovascular diseases: an update.

Mo B, Ding Y, Ji Q Front Immunol. 2025; 16:1550226.

PMID: 40079000 PMC: 11896874. DOI: 10.3389/fimmu.2025.1550226.

Neutrophil Extracellular Traps in Atherosclerosis: Research Progress.

Shi Z, Gong S, Li Y, Yan K, Bao Y, Ning K Int J Mol Sci. 2025; 26(5).

PMID: 40076955 PMC: 11900999. DOI: 10.3390/ijms26052336.

Electroacupuncture delays the progression of juvenile collagen-induced arthritis via regulation NLRP3/ NF-κB signaling pathway -mediated pyroptosis and its influence on autophagy.

Khadour F, Khadour Y, Xu T Clin Rheumatol. 2025; .

PMID: 40067573 DOI: 10.1007/s10067-025-07354-7.

References

Takeuchi O, Akira S . MDA5/RIG-I and virus recognition. Curr Opin Immunol. 2008; 20(1):17-22. DOI: 10.1016/j.coi.2008.01.002. View

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

Meylan E, Tschopp J, Karin M . Intracellular pattern recognition receptors in the host response. Nature. 2006; 442(7098):39-44. DOI: 10.1038/nature04946. View

Martinon F, Mayor A, Tschopp J . The inflammasomes: guardians of the body. Annu Rev Immunol. 2009; 27:229-65. DOI: 10.1146/annurev.immunol.021908.132715. View

Ohta S, Bahrun U, Shimazu R, Matsushita H, Fukudome K, Kimoto M . Induction of long-term lipopolysaccharide tolerance by an agonistic monoclonal antibody to the toll-like receptor 4/MD-2 complex. Clin Vaccine Immunol. 2006; 13(10):1131-6. PMC: 1595322. DOI: 10.1128/CVI.00173-06. View

Halle A, Hornung V, Petzold G, Stewart C, Monks B, Reinheckel T . The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008; 9(8):857-65. PMC: 3101478. DOI: 10.1038/ni.1636. View

Fernandes-Alnemri T, Wu J, Yu J, Datta P, Miller B, Jankowski W . The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 2007; 14(9):1590-604. PMC: 3345951. DOI: 10.1038/sj.cdd.4402194. View

OConnor Jr W, Harton J, Zhu X, Linhoff M, Ting J . Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties. J Immunol. 2003; 171(12):6329-33. DOI: 10.4049/jimmunol.171.12.6329. View

Masters S, Simon A, Aksentijevich I, Kastner D . Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol. 2009; 27:621-68. PMC: 2996236. DOI: 10.1146/annurev.immunol.25.022106.141627. View

10.

Anderson J, Mueller J, Misaghi A, Anderson S, Sivagnanam M, Kolodner R . Initial description of the human NLRP3 promoter. Genes Immun. 2008; 9(8):721-6. PMC: 4477692. DOI: 10.1038/gene.2008.66. View

11.

Kanneganti T, Lamkanfi M, Kim Y, Chen G, Park J, Franchi L . Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity. 2007; 26(4):433-43. DOI: 10.1016/j.immuni.2007.03.008. View

12.

Dinarello C . Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009; 27:519-50. DOI: 10.1146/annurev.immunol.021908.132612. View

13.

Roberson S, Walker W . Immortalization of cloned mouse splenic macrophages with a retrovirus containing the v-raf/mil and v-myc oncogenes. Cell Immunol. 1988; 116(2):341-51. DOI: 10.1016/0008-8749(88)90236-5. View

14.

Kahlenberg J, Lundberg K, Kertesy S, Qu Y, Dubyak G . Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis. J Immunol. 2005; 175(11):7611-22. DOI: 10.4049/jimmunol.175.11.7611. View

15.

Fernandes-Alnemri T, Yu J, Datta P, Wu J, Alnemri E . AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 2009; 458(7237):509-13. PMC: 2862225. DOI: 10.1038/nature07710. View

16.

Takeda K, Kaisho T, Akira S . Toll-like receptors. Annu Rev Immunol. 2003; 21:335-76. DOI: 10.1146/annurev.immunol.21.120601.141126. View

17.

Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey D . AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 2009; 458(7237):514-8. PMC: 2726264. DOI: 10.1038/nature07725. View

18.

Akira S, Uematsu S, Takeuchi O . Pathogen recognition and innate immunity. Cell. 2006; 124(4):783-801. DOI: 10.1016/j.cell.2006.02.015. View