IL-33通过ERK1/2信号通路促进哮喘模型小鼠气道重塑

被引:19
|
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
[1] 山东大学齐鲁医院呼吸科
[2] 兖矿集团总医院济东院区
关键词
IL-33; ERK1/2; MSK1; 支气管哮喘; 气道重塑;
D O I
10.13423/j.cnki.cjcmi.007747
中图分类号
R392.11 [免疫分子生物学(免疫化学)]; R-332 [医用实验动物学];
学科分类号
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。
引用
收藏
页码:590 / 594
页数:5
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