Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3
dc.contributor.author | Kanneganti, Thirumala-Devi | en_US |
dc.contributor.author | Ozoren, N. | en_US |
dc.contributor.author | Body-Malapel, M. | en_US |
dc.contributor.author | Amer, A. | en_US |
dc.contributor.author | Park, Jong-Hwan | en_US |
dc.contributor.author | Franchi, Luigi | en_US |
dc.contributor.author | Whitfield, J. | en_US |
dc.contributor.author | Barchet, W. | en_US |
dc.contributor.author | Colonna, M. | en_US |
dc.contributor.author | Vandenabeele, P. | en_US |
dc.contributor.author | Bertin, J. | en_US |
dc.contributor.author | Coyle, Anthony J. | en_US |
dc.contributor.author | Grant, E. P. | en_US |
dc.contributor.author | Akira, Shizuo | en_US |
dc.contributor.author | Nunez, Gabriel | en_US |
dc.date.accessioned | 2009-06-01T17:24:18Z | |
dc.date.available | 2009-06-01T17:24:18Z | |
dc.date.issued | 2006-03-09 | en_US |
dc.identifier.citation | Kanneganti, TD; Ozoren, N; Body-Malapel, M; Amer, A; Park, JH; Franchi, L; Whitfield, J; Barchet, W; Colonna, M; Vandenabeele, P; Bertin, J; Coyle, A; Grant, EP; Akira, S; Nunez, G. (2006) "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3." Nature 440(7081): 233-236. <http://hdl.handle.net/2027.42/62569> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62569 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16407888&dopt=citation | en_US |
dc.description.abstract | Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multiple-system inflammatory disease(1). Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways(2,3). Cryopyrin forms a multi-protein complex termed 'the inflammasome', which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1 beta (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1 beta and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-alpha and IL-6, as well as activation of NF-kappa B and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1 beta and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes. | en_US |
dc.format.extent | 459171 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3 | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Ctr Comprehens Canc, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA | en_US |
dc.contributor.affiliationother | Univ Ghent, Dept Mol Biomed Res, B-9052 Zwijnaarde, Belgium | en_US |
dc.contributor.affiliationother | Millennium Pharmaceut Inc, Cambridge, MA 02139 USA | en_US |
dc.contributor.affiliationother | Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 5650871, Japan | en_US |
dc.identifier.pmid | 16407888 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62569/1/nature04517.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature04517 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | bclx@med.umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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