{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ho K"],"funding":["NIEHS NIH HHS","NHLBI NIH HHS","College of Medicine Office of Research, Ohio State University","National Institutes of Health"],"pagination":["116341"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9840700"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["459"],"pubmed_abstract":["Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O<sub>3</sub>), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O<sub>3</sub> and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O<sub>3</sub> are associated with increased asthma exacerbations. To identify mechanisms by which O<sub>3</sub> 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 O<sub>3</sub> (DRAO<sub>3</sub>). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O<sub>3</sub> following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O<sub>3</sub> exposure resulted in neutrophilia. Additionally, O<sub>3</sub> 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-O<sub>3</sub> group suggesting that the lack of these immune cells may influence O<sub>3</sub>-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 O<sub>3</sub> exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations."],"journal":["Toxicology and applied pharmacology"],"pubmed_title":["Ozone impairs endogenous compensatory responses in allergic asthma."],"pmcid":["PMC9840700"],"funding_grant_id":["R01ES028829","R01 ES028829","R01 HL141217"],"pubmed_authors":["Jelic D","Lee H","Hartzler-Lovins H","Gowdy KM","Shamsi S","Ballinger MN","Ho K","Weimar D","Dunigan-Russell K","Shalosky E","Novak CM","Torres-Matias G","Englert JA","Yaeger M"],"additional_accession":[]},"is_claimable":false,"name":"Ozone impairs endogenous compensatory responses in allergic asthma.","description":"Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O<sub>3</sub>), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O<sub>3</sub> and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O<sub>3</sub> are associated with increased asthma exacerbations. To identify mechanisms by which O<sub>3</sub> 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 O<sub>3</sub> (DRAO<sub>3</sub>). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O<sub>3</sub> following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O<sub>3</sub> exposure resulted in neutrophilia. Additionally, O<sub>3</sub> 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-O<sub>3</sub> group suggesting that the lack of these immune cells may influence O<sub>3</sub>-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 O<sub>3</sub> exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-03T23:50:48.328Z","creation":"2025-04-03T23:50:48.328Z"},"accession":"S-EPMC9840700","cross_references":{"pubmed":["36502870"],"doi":["10.1016/j.taap.2022.116341"]}}