AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.

Details

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State: Public
Version: author
Serval ID
serval:BIB_29BEBCA2CFB2
Type
Article: article from journal or magazin.
Collection
Publications
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
Author(s)
Di Micco A., Frera G., Lugrin J., Jamilloux Y., Hsu E.T., Tardivel A., De Gassart A., Zaffalon L., Bujisic B., Siegert S., Quadroni M., Broz P., Henry T., Hrycyna C.A., Martinon F.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
09/08/2016
Peer-reviewed
Oui
Volume
113
Number
32
Pages
E4671-80
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.

Keywords
Animals, CARD Signaling Adaptor Proteins/physiology, Caspase 1/metabolism, DNA/metabolism, Inflammasomes/drug effects, Inflammasomes/physiology, Interleukin-1beta/secretion, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein/physiology, Nelfinavir/pharmacology, Nuclear Envelope/drug effects, Nuclear Envelope/physiology, Receptors, Interleukin-1/physiology, DNA sensors, Nelfinavir, inflammasome, nuclear envelope stress, zmpste24
Pubmed
Web of science
Open Access
Yes
Create date
28/07/2016 15:23
Last modification date
20/08/2019 14:09
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