Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction

被引:33
作者
Hauber, HP
Tsicopoulos, A
Wallaert, B
Griffin, S
McElvaney, NG
Daigneault, P
Mueller, Z
Olivenstein, R
Holroyd, KJ
Levitt, RC
Hamid, Q
机构
[1] McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada
[2] Hop Calmatte, Inst Pasteur, INSERM, U416, F-59019 Lille, France
[3] Hop Calmatte, Ctr Soins Mucoviscidose Adulte, F-59019 Lille, France
[4] Royal Coll Surgeons Ireland, Dublin 2, Ireland
[5] Montreal Chest Hosp, Montreal, PQ, Canada
[6] Genaera Corp, Plymouth Meeting, PA USA
关键词
cystic fibrosis; hCLCA1; interleukin-9; mucus;
D O I
10.1183/09031936.04.00096504
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Mucus overproduction is typical in cystic fibrosis (CF) airway disease. The human calcium-activated chloride channel, hCLCA1, has been reported to be upregulated by interleukin (IL)-9 and to regulate the expression of mucins. Therefore, the expression of IL-9, IL-9 receptor (IL-9R) and hCLCA1 between the lungs of CF patients and healthy control subjects was compared. Endoscopic biopsy samples of bronchial mucosa from 10 C F patients and six control subjects were stained with periodic acid-Schiff. IL-9, IL-9R and hCLCA1 expression was determined by immunocytochemistry. Expression of hCLCA1 mRNA was also determined by in situ hybridisation. The present study found significant increases in IL-9, IL-9R and hCLCA1 immunoreactivity, hCLCA1 mRNA expression, and numbers of mucus-producing cells in the mucosa of CF patients compared to control subjects. Positive correlations were found between IL-9R-positive-cells with IL-9-positive cells and hCLCA1-positive cells, and between PAS-positive cells with hCLCA1-positive cells and IL-9R-positive cells. Expression of hCLCA1 mRNA was colocalised with IL-9R expression and PAS-positive staining in epithelial cells. Increased expression of interleukin-9 and interleukin-9 receptor, as well as an upregulation of the human calcium-activated chloride channel, hCLCA1, in mucus-producing epithelium of cystic fibrosis patients, support the hypothesis that interleukin-9 contributes to mucus overproduction in cystic fibrosis airway disease.
引用
收藏
页码:846 / 850
页数:5
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