Epidermal growth factor system regulates mucin production in airways

摘要: Goblet-cell hyperplasia is a critical pathological feature in hypersecretory diseases of airways. However, the underlying mechanisms are unknown, and no effective therapy exists. Here we show that stimulation epidermal growth factor receptors (EGF-R) by its ligands, EGF transforming α (TGFα), causes MUC5AC expression airway epithelial cells both vitro vivo. We found MUC5AC-inducing cell line, NCI-H292, expresses EGF-R constitutively; gene was stimulated further tumor necrosis (TNFα). ligands increased at protein levels, this effect potentiated TNFα. Selective tyrosine kinase inhibitors blocked induced ligands. Pathogen-free rats expressed little cells; intratracheal instillation TNFα cells, subsequent number goblet Alcian blue–periodic acid–Schiff staining (reflecting mucous glycoconjugates), expression, whereas TNFα, EGF, or TGFα alone without effect. In sensitized rats, three instillations ovalbumin resulted goblet-cell production epithelium. Pretreatment with inhibitor, BIBX1522, prevented TNFα-EGF-R an asthma model. These findings suggest potential roles for cascade