Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma

Objective: Evidence suggests that dexamethasone involved in the apoptosis of differentiation Th17 cells, and the apoptosis of neutrophil was delayed in Neutrophilic Asthma mice model. Here we investigate the effect of dexamethasone on Th17 cells involved in the mechanisms of neutrophil asthma(NA).

Methods: NA and neutrophilic asthma dexamethasone intervention(NAD) mice were sensitized by LPS and OVA airway delivery. Eosinophilic asthma(EA) and eosinophilic asthma dexamethasone intervention(EAD) mice were sensitized through the peritoneum with OVA and aluminum hydroxide. During the challenge stage, the NA and EA mice were exposed to a 1% OVA aerosol. Before the aerosol, NAD and EAD mice were treated with 1mg/kg dexamethasone through the peritoneum. And control mice with no treatment. Data were collected after the last exposure. ELISA, flowcytometry and quantitative PCR were used to measure cytokines, TH17 cell subsets, intracellular cytokines and signaling molecule. Invasive measurements of airway resistance were used to measure airway hyperreactivity(AHR).

Results: (1) BALF IL-6 levels in NAD groups were no significant difference compared with the NA and EAD group, but all were higher than in control. (2) BALF TGF-β levels in NAD groups were no significant difference compared in NA and EAD group, but all were markedly higher in control. (3) BALF IL-7 levels in NAD groups were no significant difference with the NA group, but both were markedly higher in control. (4) The RORγt-mRNA expression levels in NAD group were markedly down-regulated compared with NA group, and were no significant difference with the EAD group and control. (5) The SOCS3-mRNA levels in the NAD group were markedly up-regulated compared with the NA and control, but were markedly down-regulated compared with EAD group. (6) The IL-7-mRNA expression levels in NAD group were markedly up-regulated compared with NA group, and was markedly higher than in EAD and control. (7) The SOCS1-mRNA levels in the NAD group were no significant difference with the NA group. And the NAD group were significant down-regulated compared with the EAD group. (8) The Th17⁺STAT5⁺ levels in the NAD group were markedly decrease compared with the NA group, but were markedly higher than in EAD and control. (9)The Th17⁺Bcl-2⁺ levels in NAD group were markedly decrease compared with the NA group, but were markedly higher thanin EAD and control. (10) The Th17⁺Caspase3⁺ levels in the NAD group were markedly decrease compared with the NA group, but were markedly lower than in EAD group and NAD group.

Conclusions: Dexamethasone can decrease the differentiation of Th17 cells to dominant down-regulated the RORγt and up-regulated the SOCS3 in NA mice. After treat with dexamethasone, high level of IL-7 can inhibit apoptosis and promote their survival of Th17 cells, connected to dominant of JAK-STAT5 signal pathway and Bcl-2, Caspase-3.