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

Kiyoshi Takeyama, Birgit Jung, Jae Jeong Shim, Pierre Regis Burgel, Trang Dao-Pick, Iris F. Ueki, Ursula Protin, Peer Kroschel, Jay A. Nadel

    Research output: Contribution to journalArticlepeer-review

    223 Citations (Scopus)

    Abstract

    Mucus hypersecretion from hyperplastic airway goblet cells is a hallmark of chronic obstructive pulmonary disease (COPD). Although cigarette smoking is 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 vitro and in vivo. In the airway epithelial cell line NCI-H292, exposure to cigarette smoke upregulated the EGFR mRNA expression and induced activation of EGFR-specific tyrosine phosphorylation, resulting in upregulation of MUC5AC mRNA and protein production, effects that were inhibited completely by selective EGFR tyrosine kinase inhibitors (BIBX1522, AG-1478) and that were decreased by antioxidants. In vivo, cigarette smoke inhalation increased MUC5AC mRNA and goblet cell production in rat airways, effects that were prevented by pretreatment with BIBX1522. These effects may explain the goblet cell hyperplasia that occurs in COPD and may provide a novel strategy for therapy in airway hypersecretory diseases.

    Original languageEnglish
    Pages (from-to)L165-L172
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Volume280
    Issue number1 24-1
    DOIs
    Publication statusPublished - 2001 Jan

    Keywords

    • Airway epithelial differentiation
    • Human goblet factor

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology

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