Increased expression of the calcium-activated chloride channel hCLCA1 in airways of patients with obstructive chronic bronchitis.
BACKGROUND
Interleukin (IL)-9 and its effect on enhancing the human calcium-activated chloride channel 1 (hCLCA1) expression have been shown to induce mucin production. Increased expression of hCLCA1 may, in turn, contribute to mucus overproduction in chronic obstructive pulmonary disease (COPD) with a chronic bronchitis (CB) phenotype.


OBJECTIVE
To determine the expression of IL-9, IL-9 receptor (IL-9R), hCLCA1 and mucoglycoconjugates in COPD.


METHODS
Bronchial biopsies were obtained from six patients with obstructive CB and six healthy control subjects. IL-9, IL-9R and hCLCA1 expression were detected using immunohistochemistry. Additionally, in situ hybridization was performed to determine the expression of hCLCA1 messenger RNA. Mucin production was assessed using periodic acid-Schiff staining.


RESULTS
There was a significantly higher number of IL-9 immunoreactive cells in the submucosa of patients with COPD than that of healthy control subjects (P<0.05). Also, a significant increase in the expression of IL-9R, hCLCA1 (protein and messenger RNA) and mucin (periodic acid-Schiff-positive cells) was noted in the bronchial epithelium of patients with COPD compared the control subjects (P<0.05).


CONCLUSIONS
Increased expression of IL-9, IL-9R and hCLCA1 in the bronchial mucosa of patients with obstructive CB suggests that mucus overproduction in this disease may be, at least in part, due to hCLCA1.
Hauber
Hans-Peter
HP
Meakins-Christie Laboratories, McGill University, 3626 St-Urbain Street, Montreal, Quebec H2X 2P2, Canada.
Bergeron
Celine
C
Tsicopoulos
Anne
A
Wallaert
Benoit
B
Olivenstein
Ron
R
Holroyd
Kenneth J
KJ
Levitt
Roy C
RC
Hamid
Qutayba
Q
D000368:Aged; D018118:Chloride Channels / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010503:Periodic Acid-Schiff Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*
C492109:CLCA1 protein, human; D018118:Chloride Channels