TY - JOUR T1 - Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00047-2017 VL - 3 IS - 4 SP - 00047-2017 AU - Mandy Menzel AU - Hamid Akbarshahi AU - Irma Mahmutovic Persson AU - Manoj Puthia AU - Leif Bjermer AU - Lena Uller Y1 - 2017/10/01 UR - http://openres.ersjournals.com/content/3/4/00047-2017.abstract N2 - 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.Lack of caspase-1 reduces eosinophilia and expression of Th2-upstream cytokines at experimental asthma exacerbation http://ow.ly/NPMK30eMV2E ER -