Katrien C De Grove1, Sharen Provoost1, Harald Braun2,3, Evy E Blomme1, Andrea R Teufelberger4, Olga Krysko4, Rudi Beyaert2,3, Guy G Brusselle1, Guy F Joos1, Tania Maes1. 1. Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium. 2. Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium. 3. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. 4. Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
Abstract
BACKGROUND: Clinical and experimental studies have identified a crucial role for IL-33 and its receptor ST2 in allergic asthma. Inhalation of traffic-related pollutants, such as diesel exhaust particles (DEP), facilitates the development of asthma and can cause exacerbations of asthma. However, it is unknown whether IL-33/ST2 signalling contributes to the enhancing effects of air pollutants on allergic airway responses. OBJECTIVE: We aim to investigate the functional role of IL-33/ST2 signalling in DEP-enhanced allergic airway responses, using an established murine model. METHODS: C57BL/6J mice were exposed to saline, DEP alone, house dust mite (HDM) alone or combined DEP+HDM. To inhibit IL-33 signalling, recombinant soluble ST2 (r-sST2) was given prophylactically (ie, during the whole experimental protocol) or therapeutically (ie, at the end of the experimental protocol). Airway hyperresponsiveness and the airway inflammatory responses were assessed in bronchoalveolar lavage fluid (BALF) and lung. RESULTS: Combined exposure to DEP+HDM increased IL-33 and ST2 expression in lung, elevated inflammatory responses and bronchial hyperresponsiveness compared to saline, sole DEP or sole HDM exposure. Prophylactic interference with the IL-33/ST2 signalling pathway impaired the DEP-enhanced allergic airway inflammation in the BALF, whereas effects on lung inflammation and airway hyperresponsiveness were minimal. Treatment with r-sST2 at the end of the experimental protocol did not modulate the DEP-enhanced allergic airway responses. CONCLUSION: Our data suggest that the IL-33/ST2 pathway contributes to the onset of DEP-enhanced allergic airway inflammation.
BACKGROUND: Clinical and experimental studies have identified a crucial role for IL-33 and its receptor ST2 in allergic asthma. Inhalation of traffic-related pollutants, such as diesel exhaust particles (DEP), facilitates the development of asthma and can cause exacerbations of asthma. However, it is unknown whether IL-33/ST2 signalling contributes to the enhancing effects of air pollutants on allergic airway responses. OBJECTIVE: We aim to investigate the functional role of IL-33/ST2 signalling in DEP-enhanced allergic airway responses, using an established murine model. METHODS: C57BL/6J mice were exposed to saline, DEP alone, house dust mite (HDM) alone or combined DEP+HDM. To inhibit IL-33 signalling, recombinant soluble ST2 (r-sST2) was given prophylactically (ie, during the whole experimental protocol) or therapeutically (ie, at the end of the experimental protocol). Airway hyperresponsiveness and the airway inflammatory responses were assessed in bronchoalveolar lavage fluid (BALF) and lung. RESULTS: Combined exposure to DEP+HDM increased IL-33 and ST2 expression in lung, elevated inflammatory responses and bronchial hyperresponsiveness compared to saline, sole DEP or sole HDM exposure. Prophylactic interference with the IL-33/ST2 signalling pathway impaired the DEP-enhanced allergic airway inflammation in the BALF, whereas effects on lung inflammation and airway hyperresponsiveness were minimal. Treatment with r-sST2 at the end of the experimental protocol did not modulate the DEP-enhanced allergic airway responses. CONCLUSION: Our data suggest that the IL-33/ST2 pathway contributes to the onset of DEP-enhanced allergic airway inflammation.
Authors: Sharon Chinthrajah; Shu Cao; Cherie Liu; Shu-Chen Lyu; Sayantani B Sindher; Andrew Long; Vanitha Sampath; Daniel Petroni; Marco Londei; Kari C Nadeau Journal: JCI Insight Date: 2019-11-14
Authors: Rebecca K Shears; Laura C Jacques; Georgia Naylor; Lisa Miyashita; Shadia Khandaker; Filipa Lebre; Ed C Lavelle; Jonathan Grigg; Neil French; Daniel R Neill; Aras Kadioglu Journal: J Allergy Clin Immunol Date: 2020-01-23 Impact factor: 10.793
Authors: Evy E Blomme; Sharen Provoost; Elise G De Smet; Katrien C De Grove; Hannelore P Van Eeckhoutte; Joyceline De Volder; Philip M Hansbro; Matteo Bonato; Marina Saetta; Sara Ra Wijnant; Fien Verhamme; Guy F Joos; Ken R Bracke; Guy G Brusselle; Tania Maes Journal: Clin Transl Immunology Date: 2021-06-05