METHODS: Human bronchial epithelial cell lines (HBECs) were stimulated with 3% CS extract (CSE) for 24h. Autophagy inducer starvation and inhibitors, Bafilomycin A1 (BafA1, 10 nM) and Chloroquine (CQ, 10 mM), siRNAs for Atg5, Atg12, LC3B were employed to change the level of autophagyin HBE cells. AP-1 inhibitor sp600125, MitoROS specific inhibitor MitoTEMP, and siRNAs for c-Jun and GRP78 were used to address their specific roles of these pathways in smoking induced autophagy and mucus production. Mice were instilled with CSE intratracheally to mimic a smoking-induced mucus hypersecretion model. Muc5ac expression was measured by real-time PCR and immunofluorescence. LC3B, c-Fos, c-Jun, GRP78 expression were determined by Western blotting.