Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack

Autor: Enomoto, Y., Orihara, Kanami, Takamasu, T., Matsuda, A., Gon, Y., Saito, H., Ra, C., Okayama, Y.
Rok vydání: 2009
Předmět:
Asthma/metabolism/*pathology
Male
Mucin 5AC
Cell Proliferation/drug effects
Epidermal growth factor
Epithelial Cells/drug effects/metabolism/pathology
Immunology and Allergy
Epidermal growth factor receptor
Intercellular Signaling Peptides and Proteins/analysis/*metabolism/pharmacology
Recombinant Proteins/pharmacology
Phosphorylation
skin and connective tissue diseases
Child
Extracellular Signal-Regulated MAP Kinases
Signal Transduction/drug effects/physiology
Cells
Cultured
biology
Fibroblasts/drug effects/metabolism
Respiratory disease
respiratory system
Recombinant Proteins
medicine.anatomical_structure
Child
Preschool
Acute Disease
Intercellular Signaling Peptides and Proteins
Female
medicine.symptom
Proto-Oncogene Proteins c-fos
Sputum/chemistry
Signal Transduction
EGF Family of Proteins
animal structures
Adolescent
Immunology
Myocytes
Smooth Muscle
Epidermal Growth Factor/analysis/*metabolism/pharmacology
Respiratory Mucosa
Amphiregulin
Myocytes
Smooth Muscle/drug effects/metabolism
Cell Line
Extracellular Signal-Regulated MAP Kinases/drug effects/metabolism
medicine
Humans
Respiratory Mucosa/drug effects/metabolism/*pathology
Proto-Oncogene Proteins c-fos/agonists/metabolism
Asthma
Cell Proliferation
Glycoproteins
Bronchus
Epidermal Growth Factor
Mucin 5AC/agonists/metabolism
business.industry
Infant
Newborn
Sputum
Infant
Epithelial Cells
Fibroblasts
medicine.disease
respiratory tract diseases
carbohydrates (lipids)
Phosphorylation/drug effects/physiology
biology.protein
business
Glycoproteins/analysis/*metabolism/pharmacology
Respiratory tract
Zdroj: The Journal of allergy and clinical immunology. 124(5)
ISSN: 1097-6825
Popis: Background Epidermal growth factor receptor ligands, such as epidermal growth factor (EGF) and amphiregulin, may play key roles in tissue remodeling in asthma. However, the kinetics of EGF and amphiregulin secretion in the airway after an acute asthma attack and the effect of prolonged airway exposure to these ligands on airway remodeling are unknown. Objective To measure the EGF and amphiregulin concentrations in sputa obtained from patients with asthma under various conditions, and to examine the effects of EGF and amphiregulin on the proliferation or differentiation of airway structural cells. Methods Epidermal growth factor and amphiregulin levels were measured by ELISA in sputum specimens collected from 14 hospitalized children with asthma during an acute asthma attack, 13 stable outpatients with asthma, 8 healthy control children, and 7 children with respiratory tract infections. The effects of EGF and amphiregulin on the proliferation and/or differentiation of normal human bronchial epithelial cells (NHBE), bronchial smooth muscle cells (BSMC), and normal human lung fibroblasts (NHLF) were examined. Results The sputum levels of EGF were significantly higher for about a week after an acute asthma attack compared with the levels in stable subjects with asthma and control subjects. In contrast, upregulation of amphiregulin in the sputa of patients with asthma was observed only during the acute attack. EGF caused proliferation of NHBE, BSMC, and NHLF, whereas amphiregulin induced proliferation of only NHBE. Prolonged exposure of NHBE to EGF and amphiregulin induced mucous cell metaplasia in an IL-13–independent manner. Conclusion Acute asthma attacks are associated with hypersecretion of EGF and amphiregulin in the airway. Recurrent acute attacks may aggravate airway remodeling.
Databáze: OpenAIRE
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