Objective: To investigate the effects of budesonide (BUD) on the airway remodeling and the expression of Janus protein tyrosine kinases 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) in asthma.
Methods: Thirty female Balb/c mice were randomly divided into 3 equal groups: control group; asthma group, sensitized on day 1, 8, and 15 and challenged from day 21 to 52 with periodically repeated intranasal drip of ovalbumin (OVA); and BUD treated group, undergoing intranasal drip of OVA as mentioned above and intranasal administration of BUD 2 hours before each OVA challenge. 24 h after the final OVA inhalation an invasive single-chamber whole body plethysmograph was used to assess the airway responsiveness. Then bronchoalveolar lavage fluid (BALF) was obtained and ELISA was used to measure the contents of interleukin (IL)-4 and IL-13. The mice were killed and their lungs taken out. HE staining and periodic acid Schiff (PAS) staining were used to observe the airway score of goblet cells. Peribronchiolar collagen deposition was imaged in Masson-stained lung sections. Biochemical assay was used to determine the total lung tissue level of collagen. Potass hydrolyse method was used to examine the content of hydroxyproline in the lung tissue. Western blotting was used to detect the protein expression of alpha-smooth muscle actin (SMA), JAK1, and STAT6. RT-PCR was used to detect the mRNA expression of alpha-SMA.
Results: The value of LogPC100 of the asthma group was 1.88 +/- 0.34, significantly higher than those of the BUD and control groups (1.79 +/- 0.18 and 0.82 +/- 0.78 respectively, both P = 0.000). The airway score of goblet cells of the asthma group was 3.05 +/- 0.23, significantly higher than those of the BUD and control groups (1.35 +/- 0.26 and 0.40 +/- 0.13 respectively, both P < 0.01). The hydroxyproline content of the asthma group was (459 +/- 47) microg/100 mg tissue, significantly higher than those of the BUD and control groups [(284 +/- 16) and (181 +/- 22) microg/100 mg tissue respectively, both P < 0.01]. The level of IL-4 of the asthma group was (14.4 +/- 1.12) ng/L, significantly higher than those of the BUD and control groups [(7.3 +/- 0.6) and (5.6 +/- 0.8) ng/L respectively, both P < 0.01]. The IL-13 level of the asthma group was (16.8 +/- 0.9) ng/L, significantly higher than those of the BUD and control groups [(10.6 +/- 0.9) and (5.6 +/- 0.8) ng/L respectively, both P < 0.01]. Treatment of BUD attenuated the allergen-induced airway hyperresponsiveness (AHR) and structural changes in airway, and decreased the values of the airway scores of goblet cells, and levels of hydroxyproline, IL-4, and IL-13 in comparison with the asthma group (all P < 0.01). Repeated OVA challenge resulted in an upregulation of the expression levels of alpha-SMA, JAK1 and STAT6 protein and alpha-SMA mRNA, while use of BUD suppressed these changes. The changes of JAK1 and STAT6 expression were correlated significantly with the changes in the airway score of goblet cells, hydroxyproline content, expression level of alpha-SMA, and levels of IL-4 and IL-13 in BALF (all P < 0.05).
Conclusion: BUD ameliorates the progression of airway remodeling following prolonged allergen challenge via regulation of JAK1/STAT6 signal pathway.