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

Yukinori Enomoto, Kanami Orihara, Tetsuya Takamasu, Akio Matsuda, Yasuhiro Gon, Hirohisa Saito, Chisei Ra, Yoshimichi Okayama

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume124
Issue number5
DOIs
Publication statusPublished - 2009 Nov
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Asthma
Sputum
Epithelial Cells
Airway Remodeling
Smooth Muscle Myocytes
Fibroblasts
Amphiregulin
Ligands
Lung
Hospitalized Child
Interleukin-13
Metaplasia
Epidermal Growth Factor Receptor
Respiratory Tract Infections
Outpatients
Up-Regulation
Enzyme-Linked Immunosorbent Assay

Keywords

  • Amphiregulin
  • bronchial asthma
  • bronchial epithelial cells
  • epidermal growth factor
  • tissue remodeling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. / Enomoto, Yukinori; Orihara, Kanami; Takamasu, Tetsuya; Matsuda, Akio; Gon, Yasuhiro; Saito, Hirohisa; Ra, Chisei; Okayama, Yoshimichi.

In: Journal of Allergy and Clinical Immunology, Vol. 124, No. 5, 11.2009.

Research output: Contribution to journalArticle

Enomoto, Yukinori ; Orihara, Kanami ; Takamasu, Tetsuya ; Matsuda, Akio ; Gon, Yasuhiro ; Saito, Hirohisa ; Ra, Chisei ; Okayama, Yoshimichi. / Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 124, No. 5.
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AU - Enomoto, Yukinori

AU - Orihara, Kanami

AU - Takamasu, Tetsuya

AU - Matsuda, Akio

AU - Gon, Yasuhiro

AU - Saito, Hirohisa

AU - Ra, Chisei

AU - Okayama, Yoshimichi

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AB - 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.

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