Increased human Ca2+-activated Cl- channel 1 expression and mucus overproduction in airway epithelia of smokers and chronic obstructive pulmonary disease patients

Respiratory Research

Keishi Kubo²  Atsushi Nakanishi¹  Shigeru Morita¹  Keisaku Fujimoto³  Hiroki Iwashita¹ 

[1] Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1, Muraoka-higashi, Fujisawa, Kanagawa, 251-8555, Japan;The First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan;Department of Clinical Laboratory Sciences, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan

关键词: Airway epithelia;    Mucus production;    Smoking;    Chronic obstructive pulmonary disease (COPD);    Ca²⁺-activated Cl^- channel 1 (CLCA1);   

Others  :  1146831
DOI  :  10.1186/1465-9921-13-55

 received in 2012-03-31, accepted in 2012-06-18,  发布年份 2012

【 摘 要 】

Background

The mechanisms underlying the association between smoking and mucus overproduction remain unknown. Because of its involvement in other airway diseases, such as asthma, we hypothesized that Ca²⁺-activated Cl^- channel 1 (CLCA1) was associated with overproduction of mucus in the airways of smokers and COPD patients.

Methods

Using real-time quantitative PCR analyses, we compared the CLCA1 mRNA expression levels in induced-sputum cells from COPD patients (n = 20), smokers without COPD (n = 5), and non-smokers (n =13). We also examined the relationship between CLCA1 protein expression and mucus production in lung airway epithelia of COPD patients (n = 6), smokers without COPD (n = 7), and non-smokers (n = 7).

Results

CLCA1 mRNA expression was significantly up-regulated in the induced-sputum cells of COPD patients compared with cells of non-smokers (p = 0.02), but there was no significant difference compared with cells of smokers without COPD. Using immunostaining with an anti-CLCA1 antibody, semi-quantitative image analyses of airway epithelium demonstrated significantly increased CLCA1 expression in smokers without COPD (p = 0.02) and in COPD patients (p = 0.002) compared with non-smokers. There were significant negative correlations between CLCA1 protein expression and FEV₁/FVC (r = −0.57, p = 0.01) and %predicted FEV₁ (r = −0.56, p = 0.01). PAS staining for mucus showed that there was a significant positive correlation between CLCA1 protein expression and mucus production (r = 0.67, p = 0.001). These markers were significantly increased in smokers without COPD (p = 0.04) and in COPD patients (p = 0.003) compared with non-smokers (non-smokers < smokers ≤ COPD).

Conclusions

CLCA1 expression is significantly related to mucus production in the airway epithelia of smokers and COPD patients, and may contribute to the development and pathogenesis of COPD by inducing mucus production.

【 授权许可】

   
2012 Iwashita et al.; licensee BioMed Central Ltd.

【 图 表 】

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