Affection to differentiation of Th17 cell in bronchiolitis rat models after injectingγ-secretase inhibitor / 中国免疫学杂志

ABSTRACT

Objective:To investigate the affection to the differentiation of Th17 cell in rat models of bronchiolitis after blocking Notch signaling by γ-secretase inhibitor and provide rationale to seek new target for bronchiolitis drug treatment. Methods:The rats were randomly divided into normal group,bronchiolitis group andγ-secretase inhibitor group. The model of bronchiolitis was established successfully by nasal dripping,and γ-secretase inhibitor(MW167) was injected into the vena caudalis. The pathological changes of the airway were observed by HE staining;the plasma level of interleukin17 ( IL-17 ) was detected by ELISA;the level of RORγt mRNA in lung tissues and peripheral blood mononuclear cells( PBMCs) was tested by real-time quantitative PCR;the levels of Notch signaling and RORγt protein in lung tissues were examined by Western blot. Results:Compared to the bronchiolitis group, the histopathologic change in MW167 intravenous injection group was significantly alleviated;the plasma level of IL-17 was decreased;the level of RORγt mRNA in lung tissues and PBMCs was lower in MW167-treated group than bronchiolitis group;the levels of Notch signaling and RORγt were decreased. Conclusion:γ-secretase inhibitor through intravenous injection suppresses the differentiation of Th17 cell and relieves the airway inflammation of bronchiolitis in rat models after blocking Notch signaling and has potential therapeutic value for treating bron-chiolitis.