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cutting edge: cias1/cryopyrin/pypaf1/nalp3/ caterpiller 1.1 is an inducible inflammatory mediator with nf- b suppressive properties


作者单位:Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599

【摘要】  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- 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- -induced activation of nf- b reporter activity. furthermore, cias1 suppressed tnf- -induced nuclear translocation of endogenous p65. transcriptional activity of exogenous nf- b 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- b-dependent proinflammatory signals.

【关键词】  cias/cryopyrin/pypaf/nalp/ caterpiller inducible inflammatory mediator suppressive properties

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