Inhibition of airway inflammation and hyperresponsiveness by budesonide via upregulation of indoleamine 2,3 dioxygenase in a murine model of acute asthma

Abstract

Objective To investigate the inhibitory effects of aerosol budesonide on the expression of indoleamine 2,3 dioxygenase (IDO),airway inflammation,and airway hyperresponsiveness in a murine model of bronchial asthma (asthma).Methods 18 BALB/c mice were randomly divided into 3 groups,including the control group,ovalbumin (OVA) group and budesonide group.Mice were sensitized and challenged by OVA.24 h after the last challenge,airway responsiveness to acetylcholine chloride (Ach) was measured.Hematoxylin & eosin staining was used to assess the inflammatory cell infiltrates.Levels of Th2 cytokines (IL-4 and IL-13) in bronchoalveolar lavage fluid (BALF),and total IgE and OVA-specific IgE (OVA-sIgE) in serum were relevantly detected by ELISA.The protein expression of IDO was determined by western blot analysis.Results The airway resistance in the OVA group was obviously increased in a dose-dependent manner following administration of Ach,whereas only a slight increase could be detected in the control group.Treatment with budesonide led to a sharp decrease in airway resistance compared with the OVA group (P ＜0.05).Total IgE and OVA-sIgE in serum,total inflammatory cells and differential eosinophils as well as Th2 cytokines in BALF were significantly increased in the OVA group.These inflammatory indices were remarkably decreased by treatment with budesonide (P ＜0.05).The pulmonary expression of IDO was apparently declined in the OVA group.Treatment with budesonide enhanced the pulmonary expression of IDO in comparison with the OVA group (P ＜ 0.05).Conclusions Budesonide could inhibit the airway inflammation and hyperresponsiveness by upregulating the expression of IDO in allergic asthma. Key words: Bronchial asthma; Indoleamine 2,3 dioxygenase; Budesonide; Dendritic cell; Regulatory T cell