Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model

Background: The aim of this study was to investigate the expression of muscarinic receptors and resultantly the effect of muscarinic antagonist, tiotropium bromide depending on aging process in a murine model of chronic asthma. Methods: Different aged female BALB/c (6 weeks old, 9 and 15 months old) female BALB/c mice were sensitized and challenged with ovalbumin (OVA) about for three months. Tiotroipum bromide of 0.1 mM was administered via intranasal route before OVA challenge. We measured cell counts and Th2 cytokines in bronchoalveolar lavage fluid and airway hyperresponsiveness. Parameters of airway remodeling and the expression of muscarinic receptor subtypes, M2/M3, were assessed. Results: Airway resistance decreased in aged ((9 and 15 months old) OVA group than young (6 weeks old) OVA group. Inflammatory cells including eosinophils had a decreased tendency according to age among the OVA groups. Administration of tiotropium showed the improvement of the infiltration of inflammatory cells and Th2 cytokines such as IL-4 and IL-13. Goblet cell hyperplasia and smooth muscle hypertrophy, pivotal markers of airway remodeling, ameliorated in the tiotropium treated group than OVA group in the three aged group. The OVA group had an increased expression of M3 subtype and a decreased expression of M2 subtype according to age. Conclusion: This study shows that tiotropium bromide could have the effect on not only airway inflammation but also remodeling regardless of age and the effect might be related with the pattern of expression of muscarinic receptors subtype.