SGK1 enhances Th9 cell differentiation and airway inflammation through NF-κB signaling pathway in asthma
2020
Wu, Xinqi | Jiang, Wei | Wang, Xiaoli | Zhang, Chi | Cai, Jinlong | Yu, Shuilian | Sun, Jianhong | Tian, Zhiliang
This study aimed to explore the effect of Sgk1 on Th9 differentiation and the underlying mechanism in asthma. The asthmatic mouse model induced by ovalbumin (OVA) and CD4⁺T cells which were cultured with TGF-β, IL-2, IL-4, and anti-IFN-γ were applied in vivo and in vitro, respectively. Flow cytometry, quantitative real-time PCR (qRT-PCR), and ELISA were performed to detect T-helper 9 (Th9) cells, IL-9 expression, and IL-9 release. Western blot was performed to examine phosphorylated(p)-IKKα, p-IκBα, p-p65, and IRF4 levels. Hematoxylin/eosin (H&E) staining was adopted to assess pathological changes of lung tissues. Inhibition of Sgk1 dramatically reversed elevated Th9 cells and IL-9 expression in the lung tissues of asthmatic mice. In vitro, Sgk1 promoted Th9 differentiation and elevated p-IKKα, p-IκBα, p-p65, and IRF4 levels, but inhibition of IKKα/IκBα/p65 pathway and IRF4 both reversed enhanced Th9 differentiation by Sgk1. Sgk1→IKKα/IκBα/NF-κBp65→IRF4→Th9 axis may be implicated in asthma development.
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