Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD
Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD
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DOI：
10.1152/ajplung.00061.2019
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发表时间：
2019-11-01
影响因子：
4.9
通讯作者：
Lecaille, Fabien
中科院分区：
文献类型：
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作者：
Andrault, Pierre-Marie;Schamberger, Andrea C.;Lecaille, Fabien
吸烟对肺组织有显着影响，包括诱导氧化应激、炎症细胞募集以及蛋白酶/抗蛋白酶失衡。这些影响会导致组织重塑和破坏，导致慢性阻塞性肺病 (COPD) 患者肺功能丧失。组织蛋白酶 S (CatS) 是一种半胱氨酸蛋白酶，参与结缔组织和基底膜的重塑/降解。 CatS 的异常表达或活性与多种疾病有关，包括关节炎、癌症、心血管疾病和肺部疾病。然而，人们对吸烟对 CatS 表达和活性的影响及其在吸烟相关肺部疾病中的作用知之甚少。在这里，我们评估了从不吸烟者和患有或不患有慢性阻塞性肺病的吸烟者肺组织中人类 CatS 的表达和活性。尽管存在氧化环境，但与从不吸烟者相比，当前吸烟者（非慢性阻塞性肺病和慢性阻塞性肺病）的 CatS 表达和活性显着较高，并且与吸烟史呈正相关。此外，我们发现原代人支气管上皮细胞接触香烟烟雾提取物会触发 P2X7 受体的激活，进而驱动 CatS 上调。目前的数据表明，除了其他蛋白酶之外，过度的 CatS 表达和活性也会导致香烟烟雾对肺稳态的有害影响。
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.