Modulation of mucus production by interleukin-13 receptor α2 in the human airway epithelium

T. Tanabe, K. Fujimoto, M. Yasuo, K. Tsushima, K. Yoshida, H. Ise, M. Yamaya

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Abstract

Background: IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor α2 (IL-13Rα2) has been suggested to act as a 'decoy receptor' in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13Rα2 remain unclear. Objective: The aim of this study was to examine the role of IL-13Rα2 in goblet cell hyperplasia and mucus overproduction by IL-13. Methods: Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air-liquid interface (ALI) method. Results: The number of periodic acid-Schiff's (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13Rα2 significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Rα2 in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Rα1 antibody and recombinant IL-13Rα2 reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL- 13Rα2 antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti- IL-13Rα1 antibody and recombinant IL-13Rα2. IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Rα1 antibody and recombinant IL-13Rα2. In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Rα2. Conclusion: The soluble form of IL-13Rα2 may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Rα1 in NHBECs.

Original languageEnglish
Pages (from-to)122-134
Number of pages13
JournalClinical and Experimental Allergy
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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