Cutting Edge: CIAS1/Cryopyrin/PYPAF1/NALP3/ CATERPILLER 1.1 Is an Inducible Inflammatory Mediator with NF-κB Suppressive Properties
- 15 December 2003
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 171 (12) , 6329-6333
- https://doi.org/10.4049/jimmunol.171.12.6329
Abstract
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-α and ligands recognized by multiple Toll-like receptors rapidly induce CIAS1 gene expression in primary human monocytes. Transfection of full-length CIAS1 or either of two shorter, naturally occurring isoforms dramatically inhibited TNF-α-induced activation of NF-κB reporter activity. Furthermore, CIAS1 suppressed TNF-α-induced nuclear translocation of endogenous p65. Transcriptional activity of exogenous NF-κB p65 was also blocked by CIAS1. The nucleotide-binding and leucine-rich repeat regions, but not the pyrin domain of CIAS1, are responsible for this inhibition. These data suggest CIAS1/cryopyrin may act as a key regulator of inflammation, induced to dampen NF-κB-dependent proinflammatory signals.Keywords
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