Format

Send to

Choose Destination
Nature. 2006 Mar 9;440(7081):233-6. Epub 2006 Jan 11.

Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3.

Author information

1
University of Michigan Medical School, Department of Pathology and Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.

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.

PMID:
16407888
DOI:
10.1038/nature04517
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances

Publication types

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for MLibrary (Deep Blue)
Loading ...
Support Center