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