Zeng Zhilin, Li Miao, Chen Jinkun, Li Qinghai, Ning Qin, Zhao Jianping, Xu Yongjian, Xie Jungang, Yu Jun
Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease.
Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2018 Feb 28;13:703-715. doi: 10.2147/COPD.S148595. eCollection 2018.
Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease characterized by inflammatory cells activation and production of inflammatory mediators. Methyl-CpG-binding domain protein 2 (MBD2) plays an important role in diverse immunological disorders by regulating immune cell functions, such as differentiation and mediator secretion. However, the role of MBD2 in COPD remains unknown.
MBD2 protein expression in lung tissues of patients with COPD and cigarette smoke (CS)-exposed mice were evaluated by Western blot and immunohistochemistry. The role of MBD2 in cigarette smoke extract (CSE)-induction of inflammatory mediator expression in the human bronchial epithelial (HBE) cell line was assessed by silencing MBD2 expression in vitro. The involvement of signaling pathways in mediation of inflammation was tested with signaling inhibitors.
Compared with controls, MBD2 expression was distinctly reduced in the bronchial epithelium of both patients with COPD and CS-exposed mice. Moreover, MBD2 expression was decreased in HBE after CSE stimulation in vitro. Moreover, MBD2 knockdown enhanced interleukin (IL)-6 and IL-8 expression in HBE in the presence and absence of CSE treatment by the ERK signaling pathway.
MBD2 protein expression was reduced in the airway epithelium of COPD. In HBE, this reduced expression was associated with increased levels of IL-6 and IL-8 mediated by the ERK pathway. These results suggest that MBD2 could contribute to chronic airway inflammation in COPD.
慢性阻塞性肺疾病（COPD）是一种常见的炎症性肺疾病，其特征为炎症细胞活化及炎症介质产生。甲基化CpG结合域蛋白2（MBD2）通过调节免疫细胞功能，如分化和介质分泌，在多种免疫紊乱中发挥重要作用。然而，MBD2在COPD中的作用尚不清楚。
采用蛋白质免疫印迹法和免疫组织化学法评估COPD患者肺组织及香烟烟雾（CS）暴露小鼠肺组织中MBD2蛋白表达。通过体外沉默MBD2表达，评估MBD2在香烟烟雾提取物（CSE）诱导人支气管上皮（HBE）细胞系炎症介质表达中的作用。用信号抑制剂检测信号通路在炎症介导中的参与情况。
与对照组相比，COPD患者及CS暴露小鼠支气管上皮中MBD2表达明显降低。此外，体外CSE刺激后HBE中MBD2表达降低。而且，在有或无CSE处理的情况下，MBD2敲低通过ERK信号通路增强了HBE中白细胞介素（IL）-6和IL-8的表达。
COPD气道上皮中MBD2蛋白表达降低。在HBE中，这种降低的表达与ERK途径介导的IL-6和IL-8水平升高有关。这些结果表明，MBD2可能促成COPD中的慢性气道炎症。
