Title: Mechanistic Basis for Obesity-related Increases in Ozone-induced Airway Hyperresponsiveness in Mice.

Authors: Shore, Stephanie A

Published In Ann Am Thorac Soc, (2017 Nov)

Abstract: Obesity is a risk factor for asthma, especially nonallergic asthma. Ozone, a common air pollutant, is a nonallergic asthma trigger. Importantly, ozone-induced decrements in lung function are greater in obese and overweight human subjects than in lean individuals. Obese mice also exhibit exaggerated pulmonary responses to ozone. Ozone causes greater increases in pulmonary resistance, in bronchoalveolar lavage neutrophils, and in airway hyperresponsiveness in obese than in lean mice. Our data indicate that IL-33 plays a role in mediating these events. Ozone causes greater release of IL-33 into bronchoalveolar lavage fluid in obese than in lean mice. Furthermore, an antibody blocking the IL-33 receptor, ST2, attenuates ozone-induced airway hyperresponsiveness in obese but not in lean mice. Our data also indicate a complex role for tumor necrosis factor (TNF)-α in obesity-related effects on the response to ozone. In obese mice, genetic deficiency in either TNF-α or TNF-α receptor 2 augments ozone-induced airway hyperresponsiveness, whereas TNF-α receptor 2 deficiency virtually abolishes ozone-induced airway hyperresponsiveness in lean mice. Finally, obesity is known to alter the gut microbiome. In female mice, antibiotics attenuate obesity-related increases in the effect of ozone on airway hyperresponsiveness, possibly by altering microbial production of short-chain fatty acids. Asthma control is often difficult to achieve in obese patients with asthma. Our data suggest that therapeutics directed against IL-33 may ultimately prove effective in these patients. The data also suggest that dietary manipulations and other strategies (prebiotics, probiotics) that alter the microbiome and/or its metabolic products may represent a new frontier for treating asthma in obese individuals.

PubMed ID: 29161088

MeSH Terms: No MeSH terms associated with this publication