基础医学与临床 ›› 2008, Vol. 28 ›› Issue (11): 1142-1145.

• 研究论文 • 上一篇    下一篇

气道黏液高分泌的信号传导通路

吴小玲 周向东   

  1. 重庆医科大学第二附属医院呼吸内科 重庆医科大学第二附属医院呼吸内科
  • 收稿日期:2008-03-17 修回日期:2008-05-20 出版日期:2008-11-25 发布日期:2008-11-25
  • 通讯作者: 周向东

Signaling pathway in human airway mucous hypersecretion

Xiao-ling WU, Xiang-dong ZHOU   

  1. Department of Respiratory Medicine, the Second Affiliated Hospital, Chongqing University of Medical Sciences Department of Respiratory Medicine, the Second Affiliated Hospital,Chongqing University Department of Respiratory Medicine, the Second Affiliated Hospital, Chongqing University of Medical Sciences Department of Respiratory Medicine, the Second Affiliated Hospital,Chongqing University
  • Received:2008-03-17 Revised:2008-05-20 Online:2008-11-25 Published:2008-11-25
  • Contact: Xiang-dong ZHOU

摘要: 目的 探讨中性粒细胞弹性蛋白酶(NE)诱导气道黏蛋白(MUC)5AC基因表达的信号传导机制。方法 用NE刺激A549细胞,以活性氧(ROS)清除剂DMTU、组织激肽释放酶抑制剂aprotinin和表皮生长因子受体(EGFR)酪氨酸激酶抑制剂AG1478为干预条件,用RT-PCR检测MUC5AC转录水平,用ELISA和Western blot法检测表皮生长因子(EGF)、EGFR及其磷酸化水平。结果 NE刺激组MUC5ACmRNA水平显著高于对照组,同时伴有EGF浓度升高和磷酸化EGFR增加。DMTU、aprotinin和AG1478干预组MUC5AC mRNA水平与NE刺激组相比显著降低,DMTU和aprotinin干预组EGF和磷酸化EGFR也显著降低。结论 NE经EGFR信号通路诱导A549细胞MUC5AC表达,其上游途径有氧化剂、组织激肽释放酶和EGF参与。

关键词: 弹性蛋白酶, 氧化剂, 表皮生长因子受体, 黏液高分泌

Abstract: Objective To explore the upstream signal transduction pathway of neutrophil elastase(NE)-induced mucin(MUC)5AC gene expression. Methods The well cultured A549 cells were either incubated with NE alone or with the addition of DMTU, aprotinin or AG1478. The levels of MUC5AC mRNA were measured with RT-PCR. The activation of epidermal growth factor receptor(EGFR) and signaling were assessed by measuring the release of epidermal growth factor(EGF) and the phosphorylation of EGFR. Results NE increased MUC5AC gene expression accompanied by the increase of EGF and phosphorylated EGFR levels. DMTU, aprotinin and AG1478 significantly inhibited the increase of MUC5AC gene expression. DMTU and aprotinin significantly decreased the levels of EGF and phosphorylated EGFR. Conclusion NE can induce MUC5AC gene expression via EGFR signalling in A549 cells. The upper stream involves oxidants, activation of tissue kallikrein and EGF.

Key words: NE, oxidant, EGF receptor, mucus hypersecretion