Modulation of mucus production by interleukin-13 receptor alpha2 in the human airway epithelium.
BACKGROUND
IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor alpha2 (IL-13Ralpha(2)) 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-13Ralpha(2) remain unclear.


OBJECTIVE
The aim of this study was to examine the role of IL-13Ralpha(2) 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-13Ralpha(2) significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Ralpha(2) in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2) reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13Ralpha(2) 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-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Ralpha(2).


CONCLUSIONS
The soluble form of IL-13Ralpha(2) may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Ralpha(1) in NHBECs.
Tanabe
T
T
Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Fujimoto
K
K
Yasuo
M
M
Tsushima
K
K
Yoshida
K
K
Ise
H
H
Yamaya
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced; D018793:Interleukin-13 / Q000494:pharmacology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D012995:Solubility; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
D000906:Antibodies; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger