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标题：AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity
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作者：Antonia Di Micco ; Gianluca Frera ; Jérôme Lugrin 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：32
页码：E4671-E4680
DOI：10.1073/pnas.1602419113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Inflammasomes are critical sensors that convey cellular stress and pathogen presence to the immune system by activating inflammatory caspases and cytokines such as IL-1β. The nature of endogenous stress signals that activate inflammasomes remains unclear. Here we show that an inhibitor of the HIV aspartyl protease, Nelfinavir, triggers inflammasome formation and elicits an IL-1R–dependent inflammation in mice. We found that Nelfinavir impaired the maturation of lamin A, a structural component of the nuclear envelope, thereby promoting the release of DNA in the cytosol. Moreover, deficiency of the cytosolic DNA-sensor AIM2 impaired Nelfinavir-mediated inflammasome activation. These findings identify a pharmacologic activator of inflammasome and demonstrate the role of AIM2 in detecting endogenous DNA release upon perturbation of nuclear envelope integrity.
关键词：inflammasome ; nuclear envelope stress ; DNA sensors ; zmpste24 ; Nelfinavir