TY - JOUR
T1 - Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells
AU - Yasuo, Masanori
AU - Fujimoto, Keisaku
AU - Tanabe, Tsuyoshi
AU - Yaegashi, Hironobu
AU - Tsushima, Kenji
AU - Takasuna, Keiichirou
AU - Koike, Takeshi
AU - Yamaya, Mutsuo
AU - Nikaido, Toshio
PY - 2006/5
Y1 - 2006/5
N2 - Background: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. Objectives: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). Methods: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. Results: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor α1 (IL-13Rα1), and an antibody to IL-13 Rα1 also reduced the number of PAS-positive cells after exposure to IL-13. Conclusions: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.
AB - Background: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. Objectives: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). Methods: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. Results: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor α1 (IL-13Rα1), and an antibody to IL-13 Rα1 also reduced the number of PAS-positive cells after exposure to IL-13. Conclusions: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.
KW - Bronchial epithelial cells
KW - Goblet cell hyperplasia
KW - Interleukin-13
KW - MUC5AC
KW - hCLCA1
UR - http://www.scopus.com/inward/record.url?scp=33646581334&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646581334&partnerID=8YFLogxK
U2 - 10.1159/000091391
DO - 10.1159/000091391
M3 - Article
C2 - 16465045
AN - SCOPUS:33646581334
VL - 73
SP - 347
EP - 359
JO - Schweizerische Zeitschrift für Tuberkulose und Pneumonologie. Revue suisse de la tuberculose et de pneumonologie. Rivista svizzera della tubercolosi e della pneumonologia
JF - Schweizerische Zeitschrift für Tuberkulose und Pneumonologie. Revue suisse de la tuberculose et de pneumonologie. Rivista svizzera della tubercolosi e della pneumonologia
SN - 0025-7931
IS - 3
ER -