Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke
| Autor: | Iris F. Ueki, Birgit Jung, Peer Kroschel, Jae Jeong Shim, Pierre-Régis Burgel, Ursula Protin, Jay A. Nadel, Trang Dao-Pick, Kiyoshi Takeyama |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Physiology Gene Expression Respiratory Mucosa In Vitro Techniques Mucin 5AC Biology chemistry.chemical_compound Growth factor receptor Downregulation and upregulation Epidermal growth factor Physiology (medical) Internal medicine medicine Animals Humans Lung Diseases Obstructive RNA Messenger Enzyme Inhibitors Phosphorylation Receptor Goblet cell Smoking Mucin Mucins Cell Differentiation Epithelial Cells Tyrosine phosphorylation Cell Biology Protein-Tyrosine Kinases respiratory system Mucus Rats Specific Pathogen-Free Organisms ErbB Receptors medicine.anatomical_structure Endocrinology chemistry Tyrosine Goblet Cells |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 280:L165-L172 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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