IL-33通过ERK1/2信号通路促进哮喘模型小鼠气道重塑  

IL-33 promotes airway remodeling in a mouse model of asthma via ERK1/2 signaling pathway

作　　者：张元元[1] 边翠霞[2] 吴金香[1] 赵继萍[1] 王俊飞[1] 刘甜[1] 刘琳[1] 董亮[1] 

机构地区：[1]山东大学齐鲁医院呼吸科,山东济南250012 [2]兖矿集团总医院济东院区,山东济宁272072

出　　处：《细胞与分子免疫学杂志》2016年第5期590-594,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81270072)

摘　　要：目的探讨白细胞介素(IL-33)诱导支气管哮喘气道重塑的机制。方法雄性BALB/c小鼠随机分为对照组、卵清蛋白(OVA)组和IL-33中和抗体联合OVA组。HE染色观察小鼠气道重塑,免疫组织化学染色及Western blot法观察IL-33、α平滑肌肌动蛋白(α-SMA)、1型胶原蛋白(Col1)的表达,Western blot法检测细胞外信号调节激酶1/2(ERK1/2)及丝裂原和应激激活的蛋白激酶1(MSK1)的磷酸化水平;培养HLF-1人成纤维细胞,分别给予人重组IL-33(r IL-33)、ERK1/2的抑制剂U0126联合r IL-33、MSK1的抑制剂H89联合r IL-33处理;实时荧光定量PCR及Western blot法检测α-SMA与Col1的mRNA和蛋白表达水平,免疫荧光细胞化学技术观察ERK1/2及MSK1的磷酸化。结果 OVA组小鼠发生气道重塑,IL-33、α-SMA、Col1表达增加,ERK1/2及MSK1磷酸化增强;IL-33中和抗体预处理可显著降低OVA诱导的小鼠气道重塑及IL-33、α-SMA、Col1表达以及ERK1/2及MSK1的磷酸化。U0126或H89可抑制r IL-33引起的HLF-1细胞中ERK1/2及MSK1磷酸化增强及α-SMA与Col1表达增加。结论 IL-33通过ERK1/2-MSK1信号通路促进哮喘模型小鼠气道重塑。Objective To explore the role of IL-33 in asthmatic airway remodeling. Methods Male BALB/c mice were randomly divided into 3 groups： a control group, an ovalbumin （OVA） group, and an anti-IL-33 antibody combined with OVA group. The airway remodeling features in mice were observed by HE staining. In addition, the expressions of IL-33, alpha smooth muscle actin （a-SMA）, and type 1 collagen （ Coil ） in the airway of mice were detected by immunohistochemistry and Western blotting. Finally, Western blotting was used to determine the activation of extracellular signal-regulated kinase 1/2 （ERK1/2） and mitogen- and stress-activated protein kinase 1（MSK1） in the lungs of mice. In vitro, human lung fibroblasts （HLF-1） were pretreated with the ERK1/2 inhibitor U0126 or the MSKI inhibitor H89 respectively, and then treated with the human recombinant IL-33 （rIL-33）. Then real-time quantitative PCR and Western blotting were used to test the expressions of α-SMA and Coll. Immunofluorescence cytochemistry and Western blotting were also used to observe the phosphorylation of ERK1/2 and MSK1 in HLF-1 cells. Results The pre-treatment with the ERK1/2 inhibitor U0126 or anti-lL-33 antibody significantly abolished the OVA-induced airway remodeling, increased expressions of IL-33, α-SMA, Coil, and phosphorylation of ERK1/2 and MSK1 in the airway of mice. In vitro, the increased expressions ofα-SMA and Coil and the phosphorylation of ERK1/2 and MSK1 induced by rlL-33 in HLF-1 cells were markedly inhibited by the pre-treatment with U0126 or H89. Conclusion IL-33 promotes airway remodeling in asthmatic mice via the ERK1/2-MSK1 signaling pathway.

关 键 词：IL-33 ERK1/2 MSK1 支气管哮喘 气道重塑 

分 类 号：R392.11[医药卫生—免疫学] R562.25[医药卫生—基础医学]