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

摘要: Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold syndrome, Muckle-Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), product of CIAS1, is a member NOD-LRR protein family that has been linked to activation intracellular host defence signalling pathways. forms multi-protein complex termed 'the inflammasome', which contains apoptosis-associated speck-like (ASC) caspase-1, promotes caspase-1 processing pro-interleukin (IL)-1beta (ref. 4). Here we show effect cryopyrin deficiency on inflammasome function immune responses. ASC are essential for IL-1beta IL-18 production response bacterial RNA imidazoquinoline compounds R837 R848. In contrast, secretion tumour-necrosis factor-alpha IL-6, as well NF-kappaB mitogen-activated kinases (MAPKs) were unaffected by deficiency. Furthermore, Toll-like receptors control through different These results reveal critical role RNA-mediated provide insights regarding pathogenesis syndromes.