biostudies-literatureWilliams ASNIEHS NIH HHSNHLBI NIH HHS551-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC3673194biostudies-literatureUnknown121(5)<h4>Background</h4>Acute ozone (O(3)) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice.<h4>Objectives</h4>We examined the hypothesis that these augmented responses to O(3) are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13.<h4>Methods</h4>We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2(-/-)) mice, and obese Cpe(fat) and TNFR2-deficient Cpe(fat) mice (Cpe(fat)/TNFR2(-/-)), to O(3) (2 ppm for 3 hr) either with or without treatment with anti-IL-13 or left them unexposed.<h4>Results</h4>O(3)-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpe(fat) than in WT mice. In lean mice, TNFR2 deficiency ablated O(3)-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O(3)-induced AHR but reduced inflammatory cell recruitment. O(3) increased pulmonary expression of IL-13 in Cpe(fat) but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13-expressing CD(4+) cells in Cpe(fat) versus WT mice after O(3) exposure. In Cpe(fat) mice, anti-IL-13 treatment attenuated O(3)-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 Cpe(fat)/TNFR2(-/-) mice. There was no effect of anti-IL-13 treatment in WT mice.<h4>Conclusions</h4>Pulmonary responses to O(3) are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O(3) induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O(3)-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR.Environmental health perspectivesAugmented pulmonary responses to acute ozone exposure in obese mice: roles of TNFR2 and IL-13.PMC3673194F32 ES022556P30 ES000002ES-013307HL-084044R01 HL084044R01 ES013307ES-000002Chen LWurmbrand APSi HShore SAKasahara DIWilliams ASMathews JAfalseAugmented pulmonary responses to acute ozone exposure in obese mice: roles of TNFR2 and IL-13.<h4>Background</h4>Acute ozone (O(3)) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice.<h4>Objectives</h4>We examined the hypothesis that these augmented responses to O(3) are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13.<h4>Methods</h4>We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2(-/-)) mice, and obese Cpe(fat) and TNFR2-deficient Cpe(fat) mice (Cpe(fat)/TNFR2(-/-)), to O(3) (2 ppm for 3 hr) either with or without treatment with anti-IL-13 or left them unexposed.<h4>Results</h4>O(3)-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpe(fat) than in WT mice. In lean mice, TNFR2 deficiency ablated O(3)-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O(3)-induced AHR but reduced inflammatory cell recruitment. O(3) increased pulmonary expression of IL-13 in Cpe(fat) but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13-expressing CD(4+) cells in Cpe(fat) versus WT mice after O(3) exposure. In Cpe(fat) mice, anti-IL-13 treatment attenuated O(3)-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 Cpe(fat)/TNFR2(-/-) mice. There was no effect of anti-IL-13 treatment in WT mice.<h4>Conclusions</h4>Pulmonary responses to O(3) are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O(3) induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O(3)-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR.2013-01-01T00:00:00Z2013 May2021-02-20T18:26:48Z2019-03-27T01:10:51ZS-EPMC36731942343479510.1289/ehp.1205880