Abstract
BackgroundObesity augments pulmonary responses to ozone. We have reported that IL-33 contributes to these effects of obesity in db/db mice. The purpose of this study was to determine whether IL-33 also contributes to obesity-related changes in the response to ozone in mice with diet-induced obesity.MethodsMale wildtype C57BL/6 mice and mice deficient in ST2, the IL-33 receptor, were placed on chow or high fat diets for 12 weeks from weaning. Because the microbiome has been implicated in obesity-related changes in the pulmonary response to ozone, mice were either housed with other mice of the same genotype (same housed) or with mice of the opposite genotype (cohoused). Cohousing transfers the gut microbiome from one mouse to its cagemates.ResultsDiet-induced increases in body mass were not affected by ST2 deficiency or cohousing. In same housed mice, ST2 deficiency reduced ozone-induced airway hyperresponsiveness and neutrophil recruitment in chow-fed but not HFD-fed mice even though ST2 deficiency reduced bronchoalveolar lavage IL-5 in both diet groups. In chow-fed mice, cohousing abolished ST2-related reductions in ozone-induced airway hyperresponsiveness and neutrophil recruitment, but in HFD-fed mice, no effect of cohousing on these responses to ozone was observed. In chow-fed mice, ST2 deficiency and cohousing caused changes in the gut microbiome. High fat diet-feeding caused marked changes in the gut microbiome and overrode both ST2-related and cohousing-related differences in the gut microbiome observed in chow-fed mice.ConclusionOur data indicate a role for IL-33 in pulmonary responses to ozone in chow-fed but not high fat diet-fed mice and are consistent with the hypothesis that these diet-related differences in the role of IL-33 are the result of changes in the gut microbiome.
Highlights
Obesity is increasingly recognized as an important risk factor for asthma
We have recently reported a role for the microbiome in the effects of Interleukin receptor-like 1 (ST2) deficiency on O3-induced airway hyperresponsiveness (AHR) in lean male mice: compared to WT mice, ST2 deficient mice housed with other ST2-deficient mice have reduced O3-induced AHR, but housing ST2 deficient mice with WT mice reverts the magnitude of their O3-induced to that observed in WT mice [17]
Compared to WT mice, chow fed ST2−/− mice had significantly lower concentrations of peptide YY (PYY), but no other hormones were significantly affected by ST2 deficiency in chow-fed mice
Summary
Obesity is increasingly recognized as an important risk factor for asthma. Obesity increases both the prevalence and incidence of asthma [1]. In obese asthmatics, weight loss improves asthma symptoms and reduces airway hyperresponsiveness (AHR), a canonical feature of asthma [4, 5]. These effects of obesity are prominent in non-atopic asthmatics [5]. Hospital admissions and emergency room visits for asthma are higher after days when environmental O3 concentrations are elevated [6, 7] Both overweight and obesity exacerbate O3-induced decrements in lung function [9, 10] and the effects of obesity on O3-induced changes in lung function are magnified in subjects with pre-existing AHR [9]. The purpose of this study was to determine whether IL-33 contributes to obesity-related changes in the response to ozone in mice with diet-induced obesity
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