The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta - PubMed (original) (raw)

The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta

Fabio Martinon et al. Mol Cell. 2002 Aug.

Free article

Abstract

Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.

PubMed Disclaimer

Comment in

• In Retrospect: The inflammasome turns 15.
  Lamkanfi M, Dixit VM. Lamkanfi M, et al. Nature. 2017 Aug 30;548(7669):534-535. doi: 10.1038/548534a. Nature. 2017. PMID: 28858314 No abstract available.

Similar articles

• NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.
  Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. Agostini L, et al. Immunity. 2004 Mar;20(3):319-25. doi: 10.1016/s1074-7613(04)00046-9. Immunity. 2004. PMID: 15030775
• Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation.
  Stehlik C, Lee SH, Dorfleutner A, Stassinopoulos A, Sagara J, Reed JC. Stehlik C, et al. J Immunol. 2003 Dec 1;171(11):6154-63. doi: 10.4049/jimmunol.171.11.6154. J Immunol. 2003. PMID: 14634131
• The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.
  Papin S, Cuenin S, Agostini L, Martinon F, Werner S, Beer HD, Grütter C, Grütter M, Tschopp J. Papin S, et al. Cell Death Differ. 2007 Aug;14(8):1457-66. doi: 10.1038/sj.cdd.4402142. Epub 2007 Apr 13. Cell Death Differ. 2007. PMID: 17431422
• The inflammasome.
  Petrilli V, Papin S, Tschopp J. Petrilli V, et al. Curr Biol. 2005 Aug 9;15(15):R581. doi: 10.1016/j.cub.2005.07.049. Curr Biol. 2005. PMID: 16085473 Review. No abstract available.
• ASC, Ipaf and Cryopyrin/Nalp3: bona fide intracellular adapters of the caspase-1 inflammasome.
  Mariathasan S. Mariathasan S. Microbes Infect. 2007 Apr;9(5):664-71. doi: 10.1016/j.micinf.2007.01.017. Epub 2007 Jan 27. Microbes Infect. 2007. PMID: 17382568 Review.

Cited by

• Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein.
  Vajjhala PR, Mirams RE, Hill JM. Vajjhala PR, et al. J Biol Chem. 2012 Dec 7;287(50):41732-43. doi: 10.1074/jbc.M112.381228. Epub 2012 Oct 12. J Biol Chem. 2012. PMID: 23066025 Free PMC article.
• Another twist in the on and off affair between cell suicide and inflammation.
  Vaux DL. Vaux DL. Cell Death Differ. 2013 Aug;20(8):974-5. doi: 10.1038/cdd.2013.57. Cell Death Differ. 2013. PMID: 23832149 Free PMC article. No abstract available.
• AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases.
  Wang L, Sun L, Byrd KM, Ko CC, Zhao Z, Fang J. Wang L, et al. Front Immunol. 2020 Aug 13;11:1487. doi: 10.3389/fimmu.2020.01487. eCollection 2020. Front Immunol. 2020. PMID: 32903550 Free PMC article. Review.
• The inflammasomes: crosstalk between innate immunity and hematology.
  de Freitas Dutra V, Leal VNC, Pontillo A. de Freitas Dutra V, et al. Inflamm Res. 2022 Dec;71(12):1403-1416. doi: 10.1007/s00011-022-01646-3. Epub 2022 Oct 20. Inflamm Res. 2022. PMID: 36266587 Review.
• Pyroptosis in sepsis: Comprehensive analysis of research hotspots and core genes in 2022.
  Xia D, Wang S, Yao R, Han Y, Zheng L, He P, Liu Y, Yang L. Xia D, et al. Front Mol Biosci. 2022 Aug 11;9:955991. doi: 10.3389/fmolb.2022.955991. eCollection 2022. Front Mol Biosci. 2022. PMID: 36032662 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource

• Miscellaneous

  • NCI CPTAC Assay Portal