Effect Of AG490 On The Expression Of TH17 Cells And Tregs In The Mouse Model Of Neutrophilic Asthma

Objective To explore the effect of AG490 on the expression of Thl7 cells and Tregs in the mouse model of Neutrophilic Asthma.Methods 54 female C57BL mice were equally randomly divided into three groups:Neutrophilic asthma(NA)group,NA treated with AG490(NAAG)group,and normal control(NC)group.The above mice were treated as fowllow:Mice in NA group or NAAG group were sensitized by a mixture consists 100ug of ovalbumin(OVA,Grade V)and O.lug of lipopolysaccharide(LPS)via airway delivery on the experiment days 0,6,13.Once the sensitization stage were finished,mice in NA group and NAAG group were challenged consecutively by exposure to a 1% OVA aerosol produced by an inhalation delivery system for 60 minutes once a day,from day 21 to 22.Besides,NAAG mice were injected intraperitoneally with AG490 on the days 0,3,6,9,11,13,15,17 and 20 in the dose of 500ug.NA mice were injected intraperitoneally with the same volume of DMSO serving as a dissolvent for AG490.NC mice were without any treatment.At the time of 24 hours after the last challenge,all mice were disposed and relative index were measured in time.Bronchoalveolar lavage fluid(BALF)was collected and total white blood cell count was determined,and classification of proportion was determined.Lung tissue was separated and HE and PAS stain were done to obseve pathologic changes and goblet cell hyperplasia under the optical microscope.BALF IL-17A concentration was determined by means of enzyme-linked-immunosorbent serologic assay(ELISA).Percentages of Thl7 cells and Tregs in the lung tissue were determined by means of Flow cytometry(FCM).Results (1)BALF total cell count,neutrophil percentages and eosinophil percentages count in the NAAG group were significantly lower than that of the NA group (P<0.05),but were still higher than that of the NC group(each P<0.05). (2)Lung tissue pathologic changes and goblet cell hyperplasia were markedly improved in NAAG group compared with that of the NA group,but there were still significant change compared with that of the NC group.(3)BALF IL-17A concentration in the NAAG group was significantly lower than that of the NA group,but was still significantly higher than that of the NC group(each P<0.05).(4)Th17 cell percentage in the lung of the NAAG group was significantly lower than that of the NA group,but was still significantly higher than that of the NC group(each P<0.05).Tregs percentage in the lung of the NA group was significantly higher than that of the NAAG group(each P<0.05).Conclusions Airway inflammation in the mouse model of neutrophilic asthma is Significantly improved by early intervention with AG490 in the sentisization stage,which probably via up-regulating the espression of Tregs and down-regulating the espression of Th17 cells.