Dostert Catherine, Pétrilli Virginie, Van Bruggen Robin, Steele Chad, Mossman Brooke T, Tschopp Jürg
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Science. 2008 May 2;320(5876):674-7. doi: 10.1126/science.1156995. Epub 2008 Apr 10.
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-1beta 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.
吸入空气中的污染物，如石棉或二氧化硅，与肺部炎症、纤维化及肺癌有关。目前对于致病粉尘的存在是如何被识别以及慢性炎症性疾病是如何被触发的了解甚少。在此，我们表明石棉和二氧化硅可被Nalp3炎性小体感知，其随后的激活会导致白细胞介素-1β的分泌。炎性小体的激活由活性氧物质触发，活性氧物质是在颗粒吞噬过程中由NADPH氧化酶产生的。（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，Nalp3基因敲除小鼠肺部炎症细胞的募集减少，同时细胞因子的产生也较低。我们的研究结果表明Nalp3炎性小体与颗粒物相关的肺部疾病有关，并支持其作为主要促炎性“危险”受体的作用。
