Department of Pathology and Medical Biology, Laboratory of Allergology and Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Respir Res. 2013 Oct 2;14(1):97. doi: 10.1186/1465-9921-14-97.
Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.
We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.
We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae. The majority of these changes were persistent upon CSE depletion. Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers. These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β. Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells. Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.
The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD.
吸烟是 COPD 的主要危险因素，导致慢性气道炎症。我们假设香烟烟雾会引起气道上皮细胞线粒体的结构和功能变化，这对肺部炎症和 COPD 的发病机制有重要影响。
我们研究了长期吸烟的 COPD GOLD 分期 IV 患者在戒烟 6 个月后，其支气管上皮细胞系 BEAS-2B 中线粒体形态和线粒体功能、损伤/生物发生以及分裂/融合标志物的表达变化，并与年龄匹配的吸烟和不吸烟对照进行比较。
我们观察到，长期 CSE 暴露会引起线粒体结构的强烈变化，包括碎片化、分支化和嵴的数量增加。这些变化中的大多数在 CSE 耗尽后仍然存在。此外，长期 CSE 暴露显著增加了特定分裂/融合标志物（Fis1、Mfn1、Mfn2、Drp1 和 Opa1）、氧化磷酸化（OXPHOS）蛋白（复合物 II、III 和 V）和氧化应激（Mn-SOD）标志物的表达。这些变化伴随着促炎介质 IL-6、IL-8 和 IL-1β水平的升高。重要的是，COPD 原代支气管上皮细胞（PBECs）显示出与长期 CSE 暴露 BEAS-2B 细胞中观察到的相似的线粒体形态变化。此外，COPD 患者 PBECs 中特定 OXPHOS 蛋白的表达高于对照组吸烟者，线粒体应激标志物 PINK1 的表达也是如此。
COPD 上皮细胞中观察到的线粒体变化可能是长期暴露于香烟烟雾的结果，导致线粒体功能受损，可能在 COPD 的发病机制中起作用。
