Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3 - PubMed (original) (raw)
. 2006 Mar 9;440(7081):233-6.
doi: 10.1038/nature04517. Epub 2006 Jan 11.
Nesrin Ozören, Mathilde Body-Malapel, Amal Amer, Jong-Hwan Park, Luigi Franchi, Joel Whitfield, Winfried Barchet, Marco Colonna, Peter Vandenabeele, John Bertin, Anthony Coyle, Ethan P Grant, Shizuo Akira, Gabriel Núñez
Affiliations
- PMID: 16407888
- DOI: 10.1038/nature04517
Free article
Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3
Thirumala-Devi Kanneganti et al. Nature. 2006.
Free article
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. 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. 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)-1beta (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-1beta 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-kappaB 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-1beta 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.
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