Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 124, Issue 5, Pages 913-920Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.08.044
Keywords
Amphiregulin; bronchial asthma; bronchial epithelial cells; epidermal growth factor; tissue remodeling
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government [18604009, 20591195]
- Nihon University Joint Research
- National Institute of Biomedical Innovation [ID05-24]
- Grants-in-Aid for Scientific Research [20591195, 18604009] Funding Source: KAKEN
Ask authors/readers for more resources
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. (J Allergy Clin Immunol 2009;124:913-20.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available