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dc.contributor.authorWilliams, Alison Suzanneen_US
dc.contributor.authorMathews, Joel Andrewen_US
dc.contributor.authorKasahara, David Itiroen_US
dc.contributor.authorChen, Lucasen_US
dc.contributor.authorWurmbrand, Allison Patriciaen_US
dc.contributor.authorSi, Huiqingen_US
dc.contributor.authorShore, Stephanie Annen_US
dc.date.accessioned2014-02-13T19:01:23Z
dc.date.issued2013en_US
dc.identifier.citationWilliams, Alison Suzanne, Joel Andrew Mathews, David Itiro Kasahara, Lucas Chen, Allison Patricia Wurmbrand, Huiqing Si, and Stephanie Ann Shore. 2013. “Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13.” Environmental Health Perspectives 121 (5): 551-557. doi:10.1289/ehp.1205880. http://dx.doi.org/10.1289/ehp.1205880.en
dc.identifier.issn0091-6765en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11708593
dc.description.abstractBackground: Acute ozone (O3) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice. Objectives: We examined the hypothesis that these augmented responses to O3 are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13. Methods: We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2–/–) mice, and obese Cpefat and TNFR2-deficient Cpefat mice (Cpefat/TNFR2–/–), to O3 (2 ppm for 3 hr) either with or without treatment with anti–IL-13 or left them unexposed. Results: O3-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpefat than in WT mice. In lean mice, TNFR2 deficiency ablated O3-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O3-induced AHR but reduced inflammatory cell recruitment. O3 increased pulmonary expression of IL-13 in Cpefat but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13–expressing CD4+ cells in Cpefat versus WT mice after O3 exposure. In Cpefat mice, anti–IL-13 treatment attenuated O3-induced increases in pulmonary mechanics and inflammatory cell recruitment, but did not affect AHR. These effects of anti–IL-13 treatment were not observed in Cpefat/TNFR2–/– mice. There was no effect of anti–IL-13 treatment in WT mice. Conclusions: Pulmonary responses to O3 are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O3 induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O3-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR.en
dc.language.isoen_USen
dc.publisherNational Institute of Environmental Health Sciencesen
dc.relation.isversionofdoi:10.1289/ehp.1205880en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673194/pdf/en
dash.licenseLAAen_US
dc.subjectairway responsivenessen
dc.subjectbronchoalveolar lavageen
dc.subjectIL-5en
dc.subjectinflammationen
dc.subjectMIP-3αen
dc.titleAugmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13en
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalEnvironmental Health Perspectivesen
dash.depositing.authorWurmbrand, Allison Patriciaen_US
dc.date.available2014-02-13T19:01:23Z
dc.identifier.doi10.1289/ehp.1205880*
dash.contributor.affiliatedWurmbrand, Allison Patricia
dash.contributor.affiliatedShore, Stephanie


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