The inflammasome:: A molecular platform triggering activation of inflammatory caspases and processing of proIL-β
The inflammasome:: A molecular platform triggering activation of inflammatory caspases and processing of proIL-β
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DOI：
10.1016/s1097-2765(02)00599-3
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发表时间：
2002-08-01
期刊：
影响因子：
16
通讯作者：
Tschopp, J
中科院分区：
文献类型：
--
作者：
Martinon, F;Burns, K;Tschopp, J
白细胞介素（IL）-1 β通过其前体裂解产生需要caspase-1（和小鼠中的caspase-11）的活性，但参与促炎性caspase激活的机制仍然难以捉摸。在这里，我们报告的半胱天冬酶激活复合物，我们称之为炎症体的鉴定。炎性体包括胱天蛋白酶-1、胱天蛋白酶-5、Pycard/Asc和NALP 1，NALP 1是一种与NOD具有结构同源性的含Pyrin结构域的蛋白质。使用无细胞系统，我们表明，促炎性半胱天冬酶激活和proIL-1 β处理后，失去了先前的免疫耗竭Pycard。此外，Pycard在分化的THP-1细胞中的显性阴性形式的表达阻断了proIL-1 β成熟和体内LPS诱导的炎性半胱天冬酶的激活。因此，炎性小体构成了先天免疫的重要分支。
Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.