Loading...
Caspase-11 promotes allergic airway inflammation.
Zasłona, Zbigniew Flis, Ewelina Wilk, Mieszko M Carroll, Richard G Palsson-McDermott, Eva M Hughes, Mark M Diskin, Ciana Banahan, Kathy Ryan, Dylan G Hooftman, Alexander
Zasłona, Zbigniew
Flis, Ewelina
Wilk, Mieszko M
Carroll, Richard G
Palsson-McDermott, Eva M
Hughes, Mark M
Diskin, Ciana
Banahan, Kathy
Ryan, Dylan G
Hooftman, Alexander
Author
Zasłona, Zbigniew
Flis, Ewelina
Wilk, Mieszko M
Carroll, Richard G
Palsson-McDermott, Eva M
Hughes, Mark M
Diskin, Ciana
Banahan, Kathy
Ryan, Dylan G
Hooftman, Alexander
Misiak, Alicja
Kearney, Jay
Lochnit, Gunter
Bertrams, Wilhelm
Greulich, Timm
Schmeck, Bernd
McElvaney, Oliver J
Mills, Kingston H G
Lavelle, Ed C
Wygrecka, Małgorzata
Creagh, Emma M
O'Neill, Luke A J
Flis, Ewelina
Wilk, Mieszko M
Carroll, Richard G
Palsson-McDermott, Eva M
Hughes, Mark M
Diskin, Ciana
Banahan, Kathy
Ryan, Dylan G
Hooftman, Alexander
Misiak, Alicja
Kearney, Jay
Lochnit, Gunter
Bertrams, Wilhelm
Greulich, Timm
Schmeck, Bernd
McElvaney, Oliver J
Mills, Kingston H G
Lavelle, Ed C
Wygrecka, Małgorzata
Creagh, Emma M
O'Neill, Luke A J
Advisors
Editors
Other Contributors
Departments
Date
2020-02-26
Date Submitted
Keywords
RESPIRATORY DISORDER
ALLERGIES
ALLERGIES
Other Subjects
Subject Mesh
Planned Date
Start Date
Collaborators
Principal Investigators
Files
Loading...
s41467-020-14945-2.pdf
Adobe PDF, 2.18 MB
Alternative Titles
Publisher
Abstract
Activated caspase-1 and caspase-11 induce inflammatory cell death in a process termed pyroptosis. Here we show that Prostaglandin E2 (PGE2) inhibits caspase-11-dependent pyroptosis in murine and human macrophages. PGE2 suppreses caspase-11 expression in murine and human macrophages and in the airways of mice with allergic inflammation. Remarkably, caspase-11-deficient mice are strongly resistant to developing experimental allergic airway inflammation, where PGE2 is known to be protective. Expression of caspase-11 is elevated in the lung of wild type mice with allergic airway inflammation. Blocking PGE2 production with indomethacin enhances, whereas the prostaglandin E1 analog misoprostol inhibits lung caspase-11 expression. Finally, alveolar macrophages from asthma patients exhibit increased expression of caspase-4, a human homologue of caspase-11. Our findings identify PGE2 as a negative regulator of caspase-11-driven pyroptosis and implicate caspase-4/11 as a critical contributor to allergic airway inflammation, with implications for pathophysiology of asthma.
Language
en
Citation
ISSN
eISSN
2041-1723
ISBN
DOI
10.1038/s41467-020-14945-2
PMID
32103022