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Keywords:

  • bronchial asthma;
  • goblet cell hyperplasia;
  • IL-13;
  • IL-4;
  • MUC5AC;
  • normal human bronchial epithelial cells

Summary

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.