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Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB\/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12\u201314. Mice were exposed to ozone following each HDM challenge for 6\u2009h\/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N\u2009=\u20098\/sex\/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N\u2009=\u20096\/sex\/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33\u20130.51 for females and R2 = 0.20\u20130.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac117","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T19:13:08Z","timestamp":1667589188000},"page":"79-89","source":"Crossref","is-referenced-by-count":18,"title":["Alteration of glycosphingolipid metabolism by ozone is associated with exacerbation of allergic asthma characteristics in mice"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-6629","authenticated-orcid":false,"given":"Nathanial C","family":"Stevens","sequence":"first","affiliation":[{"name":"Genome Center, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veneese J","family":"Brown","sequence":"additional","affiliation":[{"name":"Center for Health and the Environment, School of Veterinary Medicine, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan C","family":"Domanico","sequence":"additional","affiliation":[{"name":"Center for Health and the Environment, School of Veterinary Medicine, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C","family":"Edwards","sequence":"additional","affiliation":[{"name":"Center for Health and the Environment, School of Veterinary Medicine, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1689-4446","authenticated-orcid":false,"given":"Laura S","family":"Van Winkle","sequence":"additional","affiliation":[{"name":"Center for Health and the Environment, School of Veterinary Medicine, University of California Davis , Davis, California 95616, USA"},{"name":"Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-8928","authenticated-orcid":false,"given":"Oliver","family":"Fiehn","sequence":"additional","affiliation":[{"name":"Genome Center, University of California Davis , Davis, California 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"2023013111335989600_kfac117-B1","volume-title":"State of the Air Report 2021","author":"American Lung Association","year":"2021"},{"key":"2023013111335989600_kfac117-B2","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1096\/fj.00-0742fje","article-title":"Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma","volume":"15","author":"Ammit","year":"2001","journal-title":"FASEB J"},{"key":"2023013111335989600_kfac117-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-017-0697-4","article-title":"Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model","volume":"18","author":"Bao","year":"2017","journal-title":"Respir. 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