is effective in various models of inflammatory and autoimmune diseases. In this study, we examined the effects of AG490 on the treatment of the mouse model of Neutrophilic Asthma(NA)。
Methods: 32 female C57BL mice were divided into NA group, NA treated with AG490（NAA）group and normal control(NC) group by means of a random
number table. NA and NAA mice were sensitized by low-dose lipopolysaccharide(LPS) and ovalbumin(OVA) airway delivery on days 0, 6
and 13. During the challenge stage, the NA and NAA mice were exposed to a 1% OVA aerosol for 60 minutes from day 21 to day 27, which was generated using an inhalation delivery system. Before the aerosol,NAA mice were treated with 500ug AG490 through the peritoneum on days 21,23,25and 27. The data were collected on the day 28. Bronchoalveolar lavage fluid (BALF) was collected and white blood cell counts was operated. Lung tissue stainning with HE,concentration of IL-17 in BALF by ELISA, expression of Bcl-2 and Caspase-3 on Th17 cells by flow cytometry were determined.
Results: The total cell, neutrophil percentages, and eosinophil percentages count in BALF of the NAA groups was lower than that of the NA group (P<0.05);Lung tissue pathologic changes were improved in NAA group compared with that of the NA group; BALF IL-17 cytokine concentrations in the NAA group was lower than that of the NA group, but was still higher than that of the NC group(P<0.05); Th17 cell percentage in the lung of the NAA group was lower than that of the NA group, but was still higher than that of the NC group(each P<0.05); The Th17+Bcl-2+expression levels in the NAA group were decrease compared with the NA group(P<0.05); The Th17+Caspase-3+ expression levels in the NAA group were higer compared with the NA group(P<0.05);
Conclusions: Airway inflammation in the mouse model of neutrophilic asthma was improved by treatment of AG490, which probably via down-regulating the espression of Th17 cells and BALF IL-17 cytokine concentrations;In the mouse model of neutrophilic asthma, AG490 can promote the apoptosis of Th17 cells, connected to dominant of JAK-STAT5 signal pathway and Bcl-2, Caspase-3.