Zhang Xin, Guo Suliang, Huang Xiaoxi, Li Biyun, Dai Huaping, Wang Chen
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital Affiliated to Capital Medical University Beijing, P. R. China.
National Clinical Research Center for Respiratory Diseases Beijing 100029, P. R. China.
Am J Transl Res. 2021 Mar 15;13(3):1209-1220. eCollection 2021.
Although inflammation and emphysema in patients with chronic obstructive pulmonary disease (COPD) can be ameliorated by antibiotics such as erythromycin, the impact of drug resistance is still controversial. We aimed to evaluate the role of F528, a new macrolide derivative without antibacterial effect, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model, as well as in a macrophage cell line. The inflammatory cell number and cell type in the BALF were counted, and the levels of cytokines in the BALF and cultured cell medium were measured by ELISA. The degree of emphysema and apoptosis was evaluated by H&E and immunohistochemical staining, respectively. The lung function of the mice was evaluated by a small animal lung function meter. Furthermore, the expression levels of MMP-2, MMP-9, and phospho-NF-κB in the cells and lung tissue were measured by Western blot and qRT-PCR. In the BALF of the CS-induced pulmonary inflammation and emphysema model, the numbers of inflammatory cells and cytokines were significantly decreased after F528 intervention. F528 intervention also significantly protected lung function from CS-induced emphysema, while the mean lining interception (MLI) of the F528-treated CS group was significantly lower than that of the vehicle-treated CS group. In addition, F528 treatment reduced the phosphorylation of NF-κB induced by smoke, and the expression of MMP-2 and MMP-9 was also obviously decreased by F528 treatment. We therefore conclude that F528 reduces cigarette smoke-induced inflammation and emphysema in vivo and in vitro through inhibition of the activation of NF-κB.
尽管慢性阻塞性肺疾病（COPD）患者的炎症和肺气肿可通过红霉素等抗生素得到改善，但耐药性的影响仍存在争议。我们旨在评估一种无抗菌作用的新型大环内酯衍生物F528在香烟烟雾（CS）诱导的小鼠模型以及巨噬细胞系中的肺部炎症和肺气肿中的作用。对支气管肺泡灌洗液（BALF）中的炎性细胞数量和细胞类型进行计数，并通过酶联免疫吸附测定（ELISA）测量BALF和培养细胞培养基中的细胞因子水平。分别通过苏木精-伊红（H&E）染色和免疫组织化学染色评估肺气肿程度和细胞凋亡情况。用小动物肺功能仪评估小鼠的肺功能。此外，通过蛋白质免疫印迹法（Western blot）和定量逆转录聚合酶链反应（qRT-PCR）测量细胞和肺组织中基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和磷酸化核因子-κB（phospho-NF-κB）的表达水平。在CS诱导的肺部炎症和肺气肿模型的BALF中，F528干预后炎性细胞数量和细胞因子显著减少。F528干预还显著保护肺功能免受CS诱导的肺气肿影响，而F528处理的CS组的平均内衬间距（MLI）显著低于载体处理的CS组。此外，F528处理降低了烟雾诱导的NF-κB磷酸化，F528处理也明显降低了MMP-2和MMP-9的表达。因此，我们得出结论，F528通过抑制NF-κB的激活在体内和体外减轻香烟烟雾诱导的炎症和肺气肿。
