Caspase-11 promotes allergic airway inflammation

Zbigniew Zasłona (), Ewelina Flis, Mieszko M. Wilk, Richard G. Carroll, Eva M. Palsson-McDermott, Mark M. Hughes, Ciana Diskin, Kathy Banahan, Dylan G. Ryan, Alexander Hooftman, Alicja Misiak, Jay Kearney, Gunter Lochnit, Wilhelm Bertrams, Timm Greulich, Bernd Schmeck, Oliver J. McElvaney, Kingston H. G. Mills, Ed C. Lavelle, Małgorzata Wygrecka, Emma M. Creagh and Luke A. J. O’Neill
Additional contact information
Zbigniew Zasłona: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Ewelina Flis: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Mieszko M. Wilk: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Richard G. Carroll: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Eva M. Palsson-McDermott: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Mark M. Hughes: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Ciana Diskin: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Kathy Banahan: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Dylan G. Ryan: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Alexander Hooftman: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Alicja Misiak: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Jay Kearney: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Gunter Lochnit: Justus Liebig University
Wilhelm Bertrams: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, Member of the German Center for Lung Research (DZL)
Timm Greulich: University Medical Center Giessen and Marburg, Philipps-University, Member of the German Center for Lung Research (DZL)
Bernd Schmeck: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, Member of the German Center for Lung Research (DZL)
Oliver J. McElvaney: Beaumont Hospital
Kingston H. G. Mills: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Ed C. Lavelle: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Małgorzata Wygrecka: Justus Liebig University
Emma M. Creagh: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin
Luke A. J. O’Neill: Trinity Biomedical Sciences Institute (TBSI)Trinity College Dublin

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14945-2

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