Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13.

Autor:	Williams, Alison Suzanne1, Mathews, Joel Andrew1, Kasahara, David Itiro1, Chen, Lucas1, Wurmbrand, Allison Patricia1, Huiqing Si1, Shore, Stephanie Ann1 sshore@hsph.harvard.edu
Předmět:	*Animal experimentation *Ozone *Environmental exposure Enzyme-linked immunosorbent assay Factor analysis Flow cytometry Inflammation Interleukins Lungs Mice Research funding Tumor necrosis factors Data analysis software Descriptive statistics
Zdroj:	Environmental Health Perspectives. May2013, Vol. 121 Issue 5, p551-557. 7p. 1 Chart, 6 Graphs.
Abstrakt:	Background: 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 CD4Cpe+ 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 Cpe-/- 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. [ABSTRACT FROM AUTHOR]
Databáze:	GreenFILE
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