Department of Respiratory Medicine, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
DNA Cell Biol. 2009 Jan;28(1):13-22. doi: 10.1089/dna.2008.0782.
Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease characterized by an abnormal inflammatory response of the lungs to noxious particles and gases. Cigarette smoking remains a major risk factor for COPD development; however, little is known about its effect on human airway smooth muscle cells (HASMCs). The aim of this study is to examine whether apoptosis is involved in cigarette smoke extract (CSE)-induced HASMC death and the molecular mechanisms underlying it. Our studies have shown that CSE increased the level of reactive oxygen species (ROS) and cell apoptosis of HASMCs in a dose- and time-dependent manner, and the ROS scavenger N-acetyl-cysteine abrogated the effect of ROS level and apoptosis on HASMCs. Further, the expression of Bax, Bad, and Fas was increased but Bcl-2 and nuclear factor-kappaB (NF-kappaB) was decreased in a dose- and time-dependent fashion in CSE-induced apoptosis in HASMCs. Taken together, CSE could inhibit the cell growth and induce apoptosis of HASMCs through both the mitochondrial pathway and death receptor pathway. Oxidative stress and inhibition of NF-kappaB expression caused by CSE may play important roles in apoptosis and inhibition of cell growth in HASMCs.
慢性阻塞性肺疾病（COPD）是一种高度流行的气道疾病，其特征是肺部对有害颗粒和气体的异常炎症反应。吸烟仍然是 COPD 发展的主要危险因素；然而，人们对其对人呼吸道平滑肌细胞（HASMC）的影响知之甚少。本研究旨在探讨细胞凋亡是否参与香烟烟雾提取物（CSE）诱导的 HASMC 死亡及其潜在的分子机制。我们的研究表明，CSE 以剂量和时间依赖的方式增加 HASMC 中活性氧（ROS）的水平和细胞凋亡，ROS 清除剂 N-乙酰半胱氨酸可阻断 ROS 水平和凋亡对 HASMC 的影响。此外，在 CSE 诱导的 HASMC 凋亡中，Bax、Bad 和 Fas 的表达呈剂量和时间依赖性增加，而 Bcl-2 和核因子-kappaB（NF-kappaB）的表达呈剂量和时间依赖性降低。综上所述，CSE 可能通过线粒体途径和死亡受体途径抑制 HASMC 的细胞生长并诱导其凋亡。CSE 引起的氧化应激和 NF-kappaB 表达的抑制可能在 HASMC 中的细胞凋亡和生长抑制中发挥重要作用。
