biostudies-literatureHo KNIEHS NIH HHSNHLBI NIH HHSCollege of Medicine Office of Research, Ohio State UniversityNational Institutes of Health116341https://www.ebi.ac.uk/biostudies/studies/S-EPMC9840700biostudies-literatureUnknown459Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O₃), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O₃ and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O₃ are associated with increased asthma exacerbations. To identify mechanisms by which O₃ exposure leads to asthma exacerbations, we developed a two-hit mouse model where mice were sensitized and challenged with three common allergens (dust mite, ragweed and Aspergillus fumigates, DRA) to induce allergic inflammation prior to exposure to O₃ (DRAO₃). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O₃ following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O₃ exposure resulted in neutrophilia. Additionally, O₃ exposure following DRA blunted anti-inflammatory and antioxidant responses. Finally, there were significantly less monocytes and innate lymphoid type 2 cells (ILC2s) in the dual challenged DRA-O₃ group suggesting that the lack of these immune cells may influence O₃-induced AHR in the setting of allergic inflammation. In summary, we developed a mouse model that mirrors some aspects of the clinical course of asthma exacerbations due to air pollution and identified that O₃ exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations.Toxicology and applied pharmacologyOzone impairs endogenous compensatory responses in allergic asthma.PMC9840700R01ES028829R01 ES028829R01 HL141217Jelic DLee HHartzler-Lovins HGowdy KMShamsi SBallinger MNHo KWeimar DDunigan-Russell KShalosky ENovak CMTorres-Matias GEnglert JAYaeger MfalseOzone impairs endogenous compensatory responses in allergic asthma.Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O₃), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O₃ and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O₃ are associated with increased asthma exacerbations. To identify mechanisms by which O₃ exposure leads to asthma exacerbations, we developed a two-hit mouse model where mice were sensitized and challenged with three common allergens (dust mite, ragweed and Aspergillus fumigates, DRA) to induce allergic inflammation prior to exposure to O₃ (DRAO₃). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O₃ following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O₃ exposure resulted in neutrophilia. Additionally, O₃ exposure following DRA blunted anti-inflammatory and antioxidant responses. Finally, there were significantly less monocytes and innate lymphoid type 2 cells (ILC2s) in the dual challenged DRA-O₃ group suggesting that the lack of these immune cells may influence O₃-induced AHR in the setting of allergic inflammation. In summary, we developed a mouse model that mirrors some aspects of the clinical course of asthma exacerbations due to air pollution and identified that O₃ exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations.2023-01-01T00:00:00Z2023 Jan2025-04-03T23:50:48.328Z2025-04-03T23:50:48.328ZS-EPMC98407003650287010.1016/j.taap.2022.116341