Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin, China (mainland).
Department of Andrology, First Hospital of Jilin University, Changchun, Jilin, China (mainland).
Med Sci Monit. 2018 Aug 17;24:5748-5753. doi: 10.12659/MSM.909864.
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow. COPD can progress to persistent decline of pulmonary function. This study explored the effect of CXCL10 on COPD induced by cigarette smoke (CS) and its underlying mechanism. MATERIAL AND METHODS Wild-type (WT) mice were randomly assigned into 3 groups: the control group, the CS group, and the intervention group. Mice in the CS group were exposed to CS and mice in the CXCL10 group were exposed to CS and CXCL10 neutralizing antibody. At 24 h after the last CS exposure, body weight and lung functions of each mouse were recorded. Mice were then anesthetized for collecting bronchoalveolar lavage fluid (BALF) and lung tissues. Levels of interleukin-6 (IL-6), keratinocyte chemotactic factor (KC), and monocyte chemoattractant protein-1 (MCP-1) in supernatant and lung homogenate were detected by ELISA and real-time PCR (RT-PCR), respectively. For in vitro experiments, human bronchial epithelial cells 16HBE were stimulated with different concentrations of cigarette smoke extract (CSE) and CXCL10. Cell viability and levels of inflammatory cytokines in the cell supernatant were detected by Cell Counting Kit-8 (CCK-8) and ELISA assay, respectively. RESULTS Our data showed significant weight loss and reduction of lung functions in mice in the CS group compared with those in the control group and intervention group. Increased levels of IL-6, KC, and MCP-1 in BALF and lung homogenate were observed in mice in the model group compared to those in the control group and intervention group. In vitro experiments also confirmed that CXCL10-neutralizing antibody can inhibit CSE-induced cell necrosis and activation of inflammatory cytokines. CONCLUSIONS Inhibited CXCL10 protects against COPD progression by decreasing secretion of inflammatory factors, which provides a new direction for the clinical prevention and treatment of COPD.
慢性阻塞性肺疾病（COPD）是一种阻塞性肺病，其特征是长期存在呼吸问题和气流不畅。COPD 可导致肺功能持续下降。本研究探讨了 CXCL10 对香烟烟雾（CS）诱导的 COPD 的作用及其潜在机制。
将野生型（WT）小鼠随机分为 3 组：对照组、CS 组和干预组。CS 组小鼠暴露于 CS 中，CXCL10 组小鼠暴露于 CS 和 CXCL10 中和抗体中。末次 CS 暴露后 24 h 记录每组小鼠的体重和肺功能。然后对小鼠进行麻醉，收集支气管肺泡灌洗液（BALF）和肺组织。通过 ELISA 和实时 PCR（RT-PCR）分别检测上清液和肺组织匀浆中白细胞介素 6（IL-6）、角质细胞趋化因子（KC）和单核细胞趋化蛋白-1（MCP-1）的水平。体外实验中，用不同浓度的香烟烟雾提取物（CSE）和 CXCL10 刺激人支气管上皮细胞 16HBE。通过细胞计数试剂盒-8（CCK-8）和 ELISA 测定细胞上清液中细胞活力和炎症细胞因子水平。
与对照组和干预组相比，CS 组小鼠体重明显减轻，肺功能下降。与对照组和干预组相比，模型组小鼠 BALF 和肺组织匀浆中 IL-6、KC 和 MCP-1 水平升高。体外实验也证实了 CXCL10 中和抗体可以抑制 CSE 诱导的细胞坏死和炎症细胞因子的激活。
抑制 CXCL10 通过减少炎症因子的分泌来防止 COPD 的进展，为 COPD 的临床防治提供了新的方向。
