Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica
Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica
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DOI：
10.1126/science.1156995
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发表时间：
2008-05-02
期刊：
影响因子：
56.9
通讯作者：
Tschopp, Jurg
中科院分区：
文献类型：
--
作者：
Dostert, Catherine;Petrilli, Virginie;Tschopp, Jurg
吸入空气中的污染物，如石棉或二氧化硅，与肺部炎症，纤维化和肺癌有关。如何识别致病性粉尘的存在以及如何引发慢性炎症性疾病还知之甚少。在这里，我们表明，石棉和二氧化硅是由Nalp 3炎性小体，其随后的激活导致白细胞介素-1 β分泌。炎性小体激活由活性氧物质触发，活性氧物质由NADPH氧化酶在颗粒吞噬作用后产生。（NADPH是烟酰胺腺嘌呤二核苷酸磷酸的还原形式。在石棉吸入模型中，Nalp 3（-/-）小鼠表现出减少炎症细胞向肺部的募集，减少细胞因子的产生。我们的研究结果暗示Nalp 3炎性体与颗粒物相关的肺部疾病有关，并支持其作为主要促炎“危险”受体的作用。
The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1 beta secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. ( NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3(-/-) mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter- related pulmonary diseases and support its role as a major proinflammatory "danger" receptor.