Title: Cigarette smoke induces overexpression of cathepsin S in active smokers with and without COPD
Abstract: <b>Background:</b> Cigarette smoking induces molecular changes within the lung, including oxidative stress, inflammatory cell recruitment and a protease/anti-protease imbalance, which contributes in part to emphysema, airway remodeling and airway obstruction. Nevertheless, little is known on cathepsin S (CatS), a cysteine protease that plays a key role in tissue remodeling (elastin degradation) during chronic inflammatory lung diseases. <b>Aims and objectives:</b> We evaluated whether cigarette smoke activity modulates CatS expression and activity in human lung tissues and in cellulo. <b>Methods:</b> Lung tissue extracts were obtained from forty-two COPD patients (current and former smokers), non-COPD smokers (n=20) and never-smokers (n=10). Primary human bronchial epithelial cells (pHBECs) were challenged by non-toxic doses of cigarette smoke extracts (CSE). CatS activity was determined using fluorogenic substrates and its protein expression was analyzed by western-blot, ELISA and immunohistochemistry studies. <b>Results:</b> CatS expression and activity increased significantly in current smokers with or without COPD compared to never and former smokers (p<0.05). Moreover CatS expression correlated positively with smoking status and negatively with lung function. Despite the presence of an oxidizing environment, CatS was found still active in lung tissue. Moreover, its expression in pHEBCs is rapidly enhanced by CSE in a dose dependent-manner and attenuated by P2X7 inhibitor. <b>Conclusion:</b> CatS participates in ECM remodeling during lung inflammation associated to tobacco.
Publication Year: 2018
Publication Date: 2018-09-15
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 2
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