白细胞介素-17A对鼻黏膜上皮细胞表达黏蛋白MUC5AC的刺激作用及分子机制  

IL-17A upregulates MUC5AC production in human nasal epithelial cells and its molecular mechanism

作　　者：白晶[1] 苗北平[2] 夏文彤[1] 韦屹[1] 李华斌[1] 熊观霞[1] 

机构地区：[1]中山大学附属第一医院耳鼻咽喉科医院,广东广州510080 [2]深圳市第二人民医院耳鼻咽喉科,广东深圳518035

出　　处：《中国耳鼻咽喉头颈外科》2013年第6期319-322,共4页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：国家自然科学基金项目(81271054)

摘　　要：目的观察重组人白细胞介素17A(interleukin-1 7 A,I L-1 7 A)刺激离体培养的人鼻黏膜上皮细胞(human nasal epithelial cells,HNECs)后黏蛋白MUC5AC mRNA的表达变化,并检测相关的信号通路。方法离体培养的HNECs经过IL-17A诱导0～6 h后,通过定量聚合酶链反应(quantitative polymerase chainreaction,Q-PCR)技术检测MUC5AC mRNA的表达变化;通过Western blot技术检测有无特异性阻断剂作用时p38信号通路的活化情况及相应MUC5AC mRNA的表达情况。结果 IL-17A在1 ng/ml即能诱导HNECs中MUC5AC的mRNA水平上调,并在浓度为100 ng/ml时达到峰值(F=48.60,P<0.01);p38信号通路在IL-17A诱导后开始活化,并在第30分钟达到最大程度,之后信号递减并趋于正常;采用p38特异性阻断剂SB203580抑制p38信号通路后,MUC5AC mRNA的上调得到抑制(F=223.8,P<0.01)。结论 IL-17A能通过p38信号通路诱导HNECs表达MUC5AC mRNA的过程,阻断p38信号通路可能作为干预由IL-17A诱导导致的气道黏液高分泌状态的一个关键靶点。OBJECTIVE To evaluate the effect of recombinant human interleukin-17A （IL-17A） on the expression of MUC5AC mRNA in cultured human nasal epithelial cells （HNECs） and examine the signaling pathway involved. METHODS Cultured HNECs were stimulated with IL-17A for 0 to 6h in different concentration in the presence or absence of p38 specific inhibitor （SB203580） . After that, MUC5AC mRNA was examined by Q-PCR, and activation of p38 signaling pathway was evaluated by Western blot analysis. RESULTS We found IL-17A was able to induce MUC5AC expression in cultured HNECs in a dose-dependent manner （F=48.60, P〈0.01 ） . After IL-17A incubation, p38 signaling pathway was activated in HNECs, and blocking p38 signaling pathway leaded to inhibition of MUC5AC expression in HNECs （F=223.8, P〈0.01） . CONCLUSION IL- 17A is able to induce MUC5AC mRNA expression in HNECs through p38 signaling pathway, and blocking p38 signaling pathway may represent a promising therapeutic method for IL-17A-mediated hypersecretion in airway diseases.

关 键 词：鼻黏膜 上皮细胞 白细胞介素17 黏蛋白类 信号传导 

分 类 号：R765[医药卫生—耳鼻咽喉科]