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Caspase-11 promotes allergic airway inflammation
Creagh, Emma; Lavelle, Edward; O'Neill, Luke; Mills, Kingston; Zas?ona, 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
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
Keyword(s): Activated caspase-1 and caspase-11; Immunology, Inflammation & Infection; ASTHMA; CASPASE; INFLAMMATION; Pyroptosis; Chronic Health Condition; Health
Publication Date:
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Citation(s): Zas?ona, 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;
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First Indexed: 2020-09-20 06:16:06 Last Updated: 2020-10-30 07:48:13