Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.
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.


OBJECTIVE
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 alpha(1) (IL-13Ralpha(1)), and an antibody to IL-13 Ralpha(1) 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.
Yasuo
Masanori
M
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Fujimoto
Keisaku
K
Tanabe
Tsuyoshi
T
Yaegashi
Hironobu
H
Tsushima
Kenji
K
Takasuna
Keiichirou
K
Koike
Takeshi
T
Yamaya
Mutsuo
M
Nikaido
Toshio
T
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000494:pharmacology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*
C492109:CLCA1 protein, human; D018118:Chloride Channels; D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger