Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model

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@article{5557af93a33244de8040a64c54f50a7e,
title = "Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model",
abstract = "Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed. Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1. Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.",
author = "Mandy Menzel and Hamid Akbarshahi and {Mahmutovic Persson}, Irma and Manoj Puthia and Leif Bjermer and Lena Uller",
year = "2017",
month = "10",
doi = "10.1183/23120541.00047-2017",
language = "English",
volume = "3",
journal = "ERJ Open Research",
issn = "2312-0541",
publisher = "European Respiratory Society",
number = "4",

}