AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

Di Micco Antonia; Frera Gianluca; Lugrin JeromeJamilloux YvanHsu Erh-TingTardivel AubryDe Gassart AudeZaffalon LeaBujisic BojanSiegert StefanieQuadroni ManfredoBroz PetrHenry ThomasHrycyna Christine A.Martinon Fabio

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

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AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

机译：AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

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Inflammasomes are critical sensors that convey cellular stress and pathogen presence to the immune system by activating inflammatory caspases and cytokines such as IL-1 beta. 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.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2016年第32期|E4671-E4680|共10页
作者
Di Micco Antonia; Frera Gianluca; Lugrin JeromeJamilloux YvanHsu Erh-TingTardivel AubryDe Gassart AudeZaffalon LeaBujisic BojanSiegert StefanieQuadroni ManfredoBroz PetrHenry ThomasHrycyna Christine A.Martinon Fabio;
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作者单位

Univ Lausanne, Ludwig Ctr Canc Res, Flow Cytometry Facil, CH-1066 Epalinges, Switzerland;

Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland;

Purdue Univ, Dept Chem, W Lafayette, IN 47907 USAUniv Lausanne, Ctr Integrat Genom, Prot Anal Facil, CH-1015 Lausanne, SwitzerlandUniv Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, SwitzerlandCtr Infectiol Res, INSERM, U1111, F-69007 Lyon, France;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
inflammasome; nuclear envelope stress; DNA sensors; zmpste24; Nelfinavir;

AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

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