School of Medicine, Johns Hopkins University, 615 N. Wolfe St., E7622, Baltimore, MD, 21205, USA.
Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., E7622, Baltimore, MD, 21205, USA.
Respir Res. 2019 Aug 20;20(1):190. doi: 10.1186/s12931-019-1164-1.
Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues.
We compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress.
We enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments.
Bronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested.
Clinicaltrials.gov : NCT01335971.
慢性阻塞性肺疾病（COPD）患者存在与疾病严重程度相关的高氧化应激。核因子红细胞 2 相关因子 2（Nrf2）定向应激反应通过上调抗氧化基因来应对烟草烟雾，从而在保护肺细胞免受氧化应激方面发挥关键作用。在不同细胞类型的肺部和替代外周组织中，对于处于活跃吸烟和前吸烟状态的 COPD 患者中 Nrf-2 调节基因，我们的知识存在关键空白。
我们比较了 COPD 活跃吸烟者和前吸烟者肺泡巨噬细胞、鼻和支气管上皮细胞以及外周血单核细胞（PBMC）中 Nrf2 和其六个靶基因的表达。我们比较了 Nrf2 及其靶基因以及氧化和炎症应激标志物的细胞类型特异性。
我们共纳入 89 例患者；与非吸烟者相比，吸烟者支气管上皮细胞中所有测量的 Nrf2 靶基因的表达均显著升高。肺泡巨噬细胞中没有升高，而其他每个隔室中只有一个升高。
与 COPD 前吸烟者相比，活跃吸烟者的支气管上皮细胞是 Nrf2 靶基因转录激活的最敏感组织，与氧化应激和炎症标志物相关。在测试的其他细胞类型中，基因表达没有一致的趋势。
Clinicaltrials.gov：NCT01335971。
