IL-33, diet-induced obesity, and pulmonary responses to ozone

Abstract

Background: Obesity 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. Methods: Male 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. Results: Diet-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 HFDfed 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. Conclusion: Our 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.

Glucagon‐like peptide‐1 receptor agonist inhibits aeroallergen‐induced activation of ILC2 and neutrophilic airway inflammation in obese mice

“…Previous studies reported that IL-33 drove airway neutrophilic responses to ozone in obese mice. 26,53 In contrast, our results…”

IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M

“…Neutrophils are also a significant source of OSM [ 37 ]. Since we did not observe Ad vector-expressed OSM mRNA levels to be affected by IL-33 deficiency (Figures 4(c) ), the decrease in OSM protein in BALF may reflect the lack of neutrophils in the IL-33 knockout [ 35 , 54 , 55 ].…”

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“…Carriers of 2KB upstream variant rs9990107 A and intron variant rs3836449 delCAGGGTGCCCCT (in the IL1RAP gene) are at a higher obesity risk [128]. In mice, a KO of Il1rl1 does not affect obesity levels on an HFD [198].…”