STAT6 inhibitor AG490 ameliorates airway remodeling in mice with bronchial asthma

Objective:To investigate the effects of JAK/STAT6 pathway in airway remodeling in the mice with bronchial asthma and influence of AG490 on airway remodeling and its mechanism.Methods:Thirty-two femal BALB/c mice were divided into four groups at random.They were control group,the asthma group,the group of AG490 intervention and the group of budesonide intervention.The mice were sensitized and challenged with ovalbumin to establish the chronical asthma model.The airway inflammation and the alteration of airway structure were observed by the means of haematoxylin-eosin(HE) and MASSON staining.The expression of p-STAT6 was examined by Western blot and immunohistochemistry analysis,while the content of cyclinD1 was detected by Western blot and RF PCR.Results:HE and MASSON's trichrome staining showed that there were bronchial smooth muscle hypertrophy,submucosa incrassation,airway stenosis,collagen fiber increase and mass inflammatiory cells infiltration in asthmatic group.In AG490 and budesonide intervention groups,the symptoms mentioned above were much more ameliorated.The Western blot analysis showed that the expression levels of p-STAT6 and cyclin D1 in asthmatic group were higher than control group(P 0.01),but were decreased in AG490 and budesonide intervention groups(P 0.01).The result of RT-PCR showed that the level of cyclinD1 mRNA in asthmatic group was higher than control group(P 0.01),and was reduced in the AG490 and budesonide intervention groups(P 0.01).Compared with the control group,the immunohistochemistry result showed that the expression of p-STAT6 was much higher in asthmatic group(P 0.01),and between them were AG490 and budesonide intervention groups(P 0.05).Conclusions:JAK/STAT6 signal pathway involved in airway inflammation and asthma remodeling.AG490 may ameliorate the progression of airway inflammation and remodeling via regulation of JAK/STAT6 signal pathway.