Cutting edge:: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties
Cutting edge:: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties
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DOI：
10.4049/jimmunol.171.12.6329
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发表时间：
2003-12-15
影响因子：
4.4
通讯作者：
Ting, JPY
中科院分区：
文献类型：
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作者：
O'Connor, W;Harton, JA;Ting, JPY
冷诱导自身炎症综合征1（CIAS1）基因的突变最近与三种慢性自身炎症性疾病相关联。这些观察结果表明CIAS1在调节炎症过程中具有重要作用。我们报道肿瘤坏死因子 -α（TNF -α）以及多种Toll样受体识别的配体可迅速诱导原代人单核细胞中CIAS1基因的表达。转染全长CIAS1或两种较短的天然异构体中的任何一种，都显著抑制TNF -α诱导的核因子 -κB（NF -κB）报告基因活性的激活。此外，CIAS1抑制TNF -α诱导的内源性p65的核转位。外源性NF -κB p65的转录活性也被CIAS1阻断。CIAS1的核苷酸结合和富含亮氨酸重复区域，而非pyrin结构域，负责这种抑制作用。这些数据表明CIAS1/ cryopyrin可能作为炎症的关键调节因子，被诱导以抑制NF -κB依赖性促炎信号。
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.