AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3576908
Author(s) Di Micco, Antonia; Frera, Gianluca; Lugrin, Jérôme; Jamilloux, Yvan; Hsu, Erh-Ting; Tardivel, Aubry; De Gassart, Aude; Zaffalon, Léa; Bujisic, Bojan; Siegert, Stefanie; Quadroni, Manfredo; Broz, Petr; Henry, Thomas; Hrycyna, Christine A; Martinon, Fabio
Author(s) at UniBasel Broz, Petr
Year 2016
Title AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity
Journal Proceedings of the National Academy of Sciences of the United States of America
Volume 113
Number 32
Pages / Article-Number E4671-80
Abstract 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.
Publisher National Academy of Sciences
ISSN/ISBN 0027-8424
edoc-URL http://edoc.unibas.ch/43806/
Full Text on edoc No
Digital Object Identifier DOI 10.1073/pnas.1602419113
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/27462105
ISI-Number WOS:000381293300015
Document type (ISI) Journal Article
 
   

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