Caspase-11 promotes allergic airway inflammation
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2020Author:
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Zasłona, Z., Flis, E., Wilk, M.M., Carroll, R.G., Palsson-McDermott, E.M., Hughes, M.M., Diskin, C., Banahan, K., Ryan, D.G., Hooftman, A., Misiak, A., Kearney, J., Lochnit, G., Bertrams, W., Greulich, T., Schmeck, B., McElvaney, O.J., Mills, K.H.G., Lavelle, E.C., Wygrecka, M., Creagh, E.M. & O'Neill, L.A.J., Caspase-11 promotes allergic airway inflammation, 2020, Nature Communications;Download Item:
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
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Author: Creagh, Emma; Lavelle, Edward; O'Neill, Luke; Mills, Kingston; 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.; Wygrecka, Małgorzata
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Activated caspase-1 and caspase-11Subject (TCD):
Immunology, Inflammation & Infection , ASTHMA , CASPASE , INFLAMMATION , PyroptosisMetadata
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