Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke

Mucus hypersecretion from hyperplastic airway goblet cells is a hallmark of chronic obstructive pulmonary disease (COPD). Although cigarette smoking i s thought to be involved in mucus hypersecretion in COPD, the mechanism by which cigarette smoke induces mucus overproduction is unknown. Here we show that activation of epidermal growth factor receptors (EGFR) is responsible for mucin production after inhalation of cigarette smoke in airways in vit ro and in vivo. In the airway epithelial cell line NCI-H292, exposure to ci garette smoke upregulated the EGFR mRNA expression and induced activation o f EGFR-specific tyrosine phosphorylation, resulting in upregulation of MUC5 AC mRNA and protein production, effects that were inhibited completely by s elective EGFR tyrosine kinase inhibitors (BIBX1522, AG-1478) and that were decreased by antioxidants. In vivo, cigarette smoke inhalation increased MU C5AC mRNA and goblet cell production in rat airways, effects that were prev ented by pretreatment with BIBX1522. These effects may explain the goblet c ell hyperplasia that occurs in COPD and may provide a novel strategy for th erapy in airway hypersecretory diseases.