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Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack.
J Allergy Clin Immunol. 2009 Nov; 124(5):913-20.e1-7.JA

Abstract

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.

Authors+Show Affiliations

Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19895983

Citation

Enomoto, Yukinori, et al. "Tissue Remodeling Induced By Hypersecreted Epidermal Growth Factor and Amphiregulin in the Airway After an Acute Asthma Attack." The Journal of Allergy and Clinical Immunology, vol. 124, no. 5, 2009, pp. 913-20.e1-7.
Enomoto Y, Orihara K, Takamasu T, et al. Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. J Allergy Clin Immunol. 2009;124(5):913-20.e1-7.
Enomoto, Y., Orihara, K., Takamasu, T., Matsuda, A., Gon, Y., Saito, H., Ra, C., & Okayama, Y. (2009). Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. The Journal of Allergy and Clinical Immunology, 124(5), 913-e1-7. https://doi.org/10.1016/j.jaci.2009.08.044
Enomoto Y, et al. Tissue Remodeling Induced By Hypersecreted Epidermal Growth Factor and Amphiregulin in the Airway After an Acute Asthma Attack. J Allergy Clin Immunol. 2009;124(5):913-20.e1-7. PubMed PMID: 19895983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. AU - Enomoto,Yukinori, AU - Orihara,Kanami, AU - Takamasu,Tetsuya, AU - Matsuda,Akio, AU - Gon,Yasuhiro, AU - Saito,Hirohisa, AU - Ra,Chisei, AU - Okayama,Yoshimichi, PY - 2009/04/08/received PY - 2009/07/23/revised PY - 2009/08/20/accepted PY - 2009/11/10/entrez PY - 2009/11/10/pubmed PY - 2009/12/16/medline SP - 913-20.e1-7 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 124 IS - 5 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/19895983/Tissue_remodeling_induced_by_hypersecreted_epidermal_growth_factor_and_amphiregulin_in_the_airway_after_an_acute_asthma_attack_ DB - PRIME DP - Unbound Medicine ER -