Cutting edge:: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties

Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene have been recently linked to three chronic autoinflammatory disorders. These observations point to an important role for CIAS1 in regulating inflammatory processes. We report that TNF-alpha and ligands recognized by multiple Toll-like receptors rapidly induce CIAS 1 gene expression in primary human monocytes. Transfection of full-length CIAS 1 or either of two shorter, naturally occurring isoforms dramatically inhibited TNF-alpha-induced activation of NF-kappaB reporter activity. Furthermore, CIAS1 suppressed TNF-alpha-induced nuclear translocation of endogenous p65 Transcriptional activity of exogenous NF-kappaB p65 was also blocked by CLAS1. The nucleotide-binding and leucine-rich repeat regions, but not the pyrin domain of CIAS1, are responsible for this inhibition. These data suggest CMS1/cryopyrin may act as a key regulator of inflammation, induced to dampen NF-kappaB-dependent proinflammatory signals.