Cardenas Victor J, Seashore Justin B, Tapryal Nisha, Ameri Moe, Rivera Rosalinda, Sharma Kabir, Hazra Tapas
Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555-0561, USA.
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.
Respir Res. 2025 Apr 28;26(1):165. doi: 10.1186/s12931-025-03251-4.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is an independent risk factor for lung cancer. Reduction in NEIL2 function, a DNA glycosylase involved in DNA repair during transcription, has been associated with an increased incidence of malignancies in humans. NEIL2 knockout mouse models have demonstrated increased inflammation and oxidative DNA damage in the lungs after exposure to an inflammatory insult, but data are lacking regarding NEIL2 function in individuals with COPD. We investigated whether NEIL2 levels and oxidative DNA damage to the transcribed genome are reduced in individuals with stable COPD and during severe acute exacerbations of COPD (AECOPD).
The study was conducted at a single center in the US. Eligible subjects underwent a one-time 30 cc venous blood draw. The population consisted of 50 adults: 16 with stable COPD, 11 hospitalized for AECOPD, and 23 individuals without lung disease (controls). We analyzed blood leukocytes for NEIL2 mRNA and DNA damage by RT‒qPCR and LA‒qPCR, respectively, in all groups. Plasma levels of seven biomarkers, CXCL1, CXCL8, CXCL9, CXCL10, CCL2, CCL11 and IL-6, were analyzed in the COPD groups using a magnetic bead panel (Millipore).
The fold change in NEIL2 mRNA levels were lower in individuals with stable COPD and AECOPD than in controls (0.72 for COPD, p = 0.029; 0.407 for AECOPD, p < 0.001). The difference in NEIL2 mRNA expression between the stable COPD group and AECOPD group was also statistically significant (p < 0.001). The fold change in DNA lesions per 10 kb of DNA was greater in the stable COPD (9.38, p < 0.001) and AECOPD (15.81, p < 0.001) groups than in the control group. The difference in fold change was also greater in the AECOPD group versus stable COPD p < 0.024). Cytokine levels were not significantly different between the COPD groups. NEIL2 levels were correlated with plasma eosinophil levels in the stable COPD group (r = 0.737, p = 0.003).
NEIL2 mRNA levels are significantly reduced in individuals with COPD and may exacerbate DNA damage and inflammation. These results suggest a possible mechanism that increases inflammation and oxidative genomic damage in COPD.
Not applicable.
慢性阻塞性肺疾病（COPD）是一种慢性炎症性气道疾病，是肺癌的独立危险因素。NEIL2是一种参与转录过程中DNA修复的DNA糖基化酶，其功能降低与人类恶性肿瘤发病率增加有关。NEIL2基因敲除小鼠模型显示，暴露于炎性刺激后，肺部炎症和氧化性DNA损伤增加，但关于COPD患者中NEIL2功能的数据尚缺乏。我们研究了稳定期COPD患者以及COPD严重急性加重期（AECOPD）患者的NEIL2水平和转录基因组的氧化性DNA损伤是否降低。
该研究在美国的一个单一中心进行。符合条件的受试者一次性采集30cc静脉血。研究人群包括50名成年人：16名稳定期COPD患者、11名因AECOPD住院的患者以及23名无肺部疾病的个体（对照组）。我们分别通过RT-qPCR和LA-qPCR分析了所有组血液白细胞中的NEIL2 mRNA和DNA损伤情况。使用磁珠板（密理博）分析了COPD组中七种生物标志物CXCL1、CXCL8、CXCL9、CXCL10、CCL2、CCL11和IL-6的血浆水平。
稳定期COPD患者和AECOPD患者的NEIL2 mRNA水平的变化倍数低于对照组（COPD组为0.72，p = 0.029；AECOPD组为0.407，p < 0.001）。稳定期COPD组和AECOPD组之间NEIL2 mRNA表达的差异也具有统计学意义（p < 0.001）。稳定期COPD组（9.38，p < 0.001）和AECOPD组（15.81，p < 0.00１）每10kb DNA的DNA损伤变化倍数高于对照组。AECOPD组与稳定期COPD组之间变化倍数的差异也更大（p < 0.024）。COPD组之间细胞因子水平无显著差异。稳定期COPD组中NEIL2水平与血浆嗜酸性粒细胞水平相关（r = 0.737，p = 0.003）。
COPD患者的NEIL2 mRNA水平显著降低，可能会加剧DNA损伤和炎症。这些结果提示了一种可能的机制，该机制会增加COPD中的炎症和氧化性基因组损伤。
不适用。
