Effect Of Dexamethasone In Th17Cell Mediating Neutrophilic Asthma

Objective: Establish the mice model of Neutrophilic Asthma(NA), EosinophilicAsthma(EA), Neutrophilic Asthma dexamethasone intervention(NAD) andEosinophilic Asthma dexamethasone intervention(EAD). To explore the effectof dexamethasone in Th17cell mediating in Neutrophilic Asthma.Methods:80female C57BL mice were divided into NA group, EA group,NAD group, EAD group and normal control(NC) group by means of a randomnumber table. NA and NAD mice were sensitized by low-doselipopolysaccharide(LPS) and ovalbumin(OVA) airway delivery on days0,6and13. EA and EAD mice were sensitized through the peritoneum with OVAand aluminum hydroxide on days0,7and14. During the challenge stage, theNA and EA mice were exposed to a1%OVA aerosol for60minutes from day21, which was generated using an inhalation delivery system. Before the aerosol,NAD and EAD mice were treated with1mg/kg dexamethasone through theperitoneum. And NC mice with no treatment. All mice except NC mice wereexposed to the aerosol treatments once per day for14consecutive days fromday21th, and the data were collected on the day after the last exposure. Bronchoalveolar lavage fluid(BALF) was collected and white blood cell countswas operated. Lung tissue stainning with HE and Periodic Acid-Schiff(PAS),concentration of TGF-β, IL-6, IL-7, KC（CXCL1）and LIX（CXCL5）in BALFby RayBiotech quantitative antibody arrays, expression of STAT5, Bcl-2andCaspase-3on Th17cell by Flow cytometry, expression of RORγt-mRNA,IL-7-mRNA, SOCS1-mRNA and SOCS3-mRNA on mice spleen by Real-timequantitative polymerase chain reaction(RT-PCR) were determined.Results:(1)A significant decrease in the total cell, neutrophil percentages, andeosinophil percentages count in BALF of the NAD and EAD groups aftertreated with dexamethasone(each P<0.05). The BALF total cell was higher inthe NAD group than in the EAD group(P<0.05).(2) The pathological changesof lung tissue in NA and EA mice were markedly improved afterdexamethasone intervention. No significant difference were found in gobletcells%between the NAD group and EAD group(P＞0.05), but both weresignificant increased compare with NC mice(each P<0.05).(3) BALF IL-6levels in the NAD groups were no significant difference compared with the NAand EAD group(each P＞0.05), bot all were markedly higher than that of theNC group(each P<0.05).(4) BALF TGF-β levels in the NAD groups were nosignificant difference compared with the NA nd EAD group(P＞0.05), but allwere markedly higher than that of the NC group(each P<0.05).(5) BALF IL-7levels in the NAD groups were no significant difference with the NA group(P＞ 0.05), but both were markedly higher than that of the NC group(each P<0.05).And it was markedly higher in NAD group than that of the EAD group(P<0.05).(6) BALF CXCL1levels in the NAD group were markedly lower than that ofthe NA and EAD group(each P<0.05), and was no significant difference withthe NC group(P＞0.05).(7) BALF CXCL5levels in the NAD group weremarkedly higher than that of the NA and EAD group(P<0.05), and both weremarkedly higher than that of the NC group(eachP<0.05).(8) The RORγt-mRNAexpression levels in the NAD group were markedly down-regulated comparedwith the NA group(P<0.05), and were no significant difference with the NC andEAD group(P＞0.05).(9) The SOCS3-mRNA expression levels in the NADgroup were markedly up-regulated compared with the NA and NC group(eachP<0.05), but were markedly down-regulated compared with EADgroup(eachP<0.05).(10) The IL-7-mRNA expression levels in the NAD groupwere markedly up-regulated compared with the NA group(P<0.05), and wasmarkedly higher than the EAD and NC group(eachP<0.05).(11) TheSOCS1-mRNA expression levels in the NAD group were no significantdifference with the NA group(P＞0.05), but both were markedlydown-regulated compared with the NC group(each P<0.05). And the NADgroup were much more significant down-regulated compared with the EADgroup(P<0.05).(12) The Th17+STAT5+expression levels in the NAD groupwere markedly decrease compared with the NA group(P<0.05), but were markedly higher than that of the EAD and NC group(each P<0.05).(13)TheTh17+Bcl-2+expression levels in the NAD group were markedly decreasecompared with the NA group(P<0.05), but were markedly higher than that ofthe EAD and NC group(each P<0.05).(14) The Th17+Caspase-3+expressionlevels in the NAD group were markedly decrease compared with the NAgroup(P<0.05), but were markedly lower than that of the EAD group(P<0.05)and NAD group was no significant difference with the NC group(P＞0.05).Conclusions: Dexamethasone can decrease the differentiation of Th17cells todominant down-regulated the RORγt and up-regulated the SOCS3in NA mice.After treat with dexamethasone, high level of IL-7can inhibit apoptosis andpromote their survival of Th17cells, connected to dominant of JAK-STAT5signal pathway and Bcl-2, Caspase-3.