Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation
| Autor: | Iris F. Ueki, Pierre-Régis Burgel, Dominic Cheng Wei Tam, Jay A. Nadel, Stephen C. Lazarus, Martha Birch, Kamran Atabai |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Immunology Inflammation In situ hybridization Respiratory Mucosa Mucin 5AC Downregulation and upregulation medicine Hypersensitivity Tumor Cells Cultured Immunology and Allergy Humans Epidermal growth factor receptor RNA Messenger Enzyme Inhibitors Phosphorylation Pulmonary Eosinophilia Cells Cultured biology Mucin Mucins respiratory system Eosinophil Middle Aged Transforming Growth Factor alpha Tyrphostins Mucus Molecular biology Epithelium Asthma Up-Regulation Eosinophils ErbB Receptors medicine.anatomical_structure Culture Media Conditioned biology.protein Quinazolines medicine.symptom |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 167(10) |
| ISSN: | 0022-1767 |
| Popis: | Eosinophil recruitment and mucus hypersecretion are characteristic of asthmatic airway inflammation, but eosinophils have not been shown to induce mucin production. Because an epidermal growth factor receptor (EGFR) cascade induces MUC5AC mucin in airways, and because EGFR is up-regulated in asthmatic airways, we examined the effect of eosinophils on MUC5AC mucin production in NCI-H292 cells (a human airway epithelial cell line that produces mucins). Eosinophils were isolated from the peripheral blood of allergic patients, and their effects on MUC5AC mucin gene and protein synthesis were assessed using in situ hybridization and ELISAs. When IL-3 plus GM-CSF or IL-3 plus IL-5 were added to eosinophils cultured with NCI-H292 cells, MUC5AC mucin production increased; eosinophils or cytokines alone had no effect. Eosinophil supernatant obtained by culturing eosinophils with IL-3 plus GM-CSF or IL-3 plus IL-5 also increased MUC5AC synthesis in NCI-H292 cells, an effect that was prevented by selective EGFR inhibitors (AG1478, BIBX1522). Supernatant of activated eosinophils induced EGFR phosphorylation in NCI-H292 cells. Supernatant of activated eosinophils contained increased concentrations of TGF-α protein (an EGFR ligand) and induced up-regulation of TGF-α expression and release in NCI-H292 cells. A blocking Ab to TGF-α reduced activated eosinophil-induced MUC5AC synthesis in NCI-H292 cells. These results show that activated eosinophils induce mucin synthesis in human airway epithelial cells via EGFR activation, and they implicate TGF-α produced by eosinophils and epithelial cells in the EGFR activation that results in mucin production in human airway epithelium. |
| Databáze: | OpenAIRE |
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