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首页> 外文期刊>Nature >Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3.
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Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3.

机译：细菌RNA和小的抗病毒化合物可通过Cypyryrin / Nalp3激活caspase-1。

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摘要

Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways. Cryopyrin forms a multi-protein complex termed 'the inflammasome', which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1beta (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1beta and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-alpha and IL-6, as well as activation of NF-kappaB and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1beta and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.
机译：CIAS1基因的错义突变会导致三种自身炎症性疾病：家族性冷性自身炎症综合症，Muckle-Wells综合征和新生儿多发性炎症。 Cryopyrin（也称为Nalp3）是CIAS1的产物，是NOD-LRR蛋白家族的成员，已与细胞内宿主防御信号通路的激活相关。隐藻蛋白形成一种称为``炎症小体''的多蛋白复合物，其中包含凋亡相关的斑点样蛋白（ASC）和caspase-1，并促进caspase-1激活和促白介素（IL）-1beta的加工（参考4）在这里，我们显示了冷敷蛋白缺乏对炎性体功能和免疫反应的影响。对于细菌RNA和咪唑并喹啉化合物R837和R848而言，隐索蛋白和ASC对于caspase-1激活以及IL-1beta和IL-18产生至关重要。相反，肿瘤坏死因子-α和IL-6的分泌，以及NF-κB和丝裂原激活的蛋白激酶（MAPKs）的激活均不受冷丝蛋白缺乏的影响。此外，我们表明，Toll样受体和冷蛋白通过不同的细胞内途径控制IL-1beta和IL-18的分泌。这些结果揭示了冷冻素通过细菌RNA介导的caspase-1活化在宿主防御中的关键作用，并提供了关于自身炎症综合征发病机理的见解。

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