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Andrault, P.-M.* ; Schamberger, A.C. ; Chazeirat, T.* ; Sizaret, D.* ; Renault, J.* ; Staab-Weijnitz, C.A. ; Hennen, E. ; Petit-Courty, A.* ; Wartenberg, M.* ; Saidi, A.* ; Baranek, T.* ; Guyetant, S.* ; Courty, Y.* ; Eickelberg, O. ; Lalmanach, G.* ; Lecaille, F.*

Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD.

Am. J. Physiol. Lung Cell Mol. Physiol. 317, L625-L638 (2019)
Postprint DOI PMC
Open Access Green
Cigarette smoking has marked effects on lung tissue, including induction of oxidative stress, inflammatory cell recruitment, and a protease/antiprotease imbalance. These effects contribute to tissue remodeling and destruction resulting in loss of lung function in chronic obstructive pulmonary disease (COPD) patients. Cathepsin S (CatS) is a cysteine protease that is involved in the remodeling/degradation of connective tissue and basement membrane. Aberrant expression or activity of CatS has been implicated in a variety of diseases, including arthritis, cancer, cardiovascular, and lung diseases. However, little is known about the effect of cigarette smoking on both CatS expression and activity, as well as its role in smoking-related lung diseases. Here, we evaluated the expression and activity of human CatS in lung tissues from never-smokers and smokers with or without COPD. Despite the presence of an oxidizing environment, CatS expression and activity were significantly higher in current smokers (both non-COPD and COPD) compared with never-smokers, and correlated positively with smoking history. Moreover, we found that the exposure of primary human bronchial epithelial cells to cigarette smoke extract triggered the activation of P2X7 receptors, which in turns drives CatS upregulation. The present data suggest that excessive CatS expression and activity contribute, beside other proteases, to the deleterious effects of cigarette smoke on pulmonary homeostasis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cigarette Smoke ; Copd ; Cysteine Protease ; Oxidation ; Smokers; Cysteine Cathepsins; Emerging Roles; Expression; Release; Macrophages; Inhibitor; Emphysema; Pathogenesis; Mechanisms; Cessation
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Journal American Journal of Physiology - Lung Cellular and Molecular Physiology
Quellenangaben Volume: 317, Issue: 5, Pages: L625-L638 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place Bethesda, Md. [u.a.]
Application country DE
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)