Wang Yan, Gao Xiaoyu, Li Yuan, Wang Xiao, Li Yuanyuan, Zhang Sainan, Liu Hongyan, Guo Hui, Lu Wenju, Sun Dejun
Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China.
Graduate School, Baotou Medical College, Baotou, Inner Mongolia, China.
Exp Physiol. 2021 May;106(5):1303-1311. doi: 10.1113/EP089244. Epub 2021 Apr 8.
What is the central question of this study? It is reported that polymorphism of the gene for pulmonary surfactant-associated protein B (SFTPB) is associated with chronic obstructive pulmonary disease (COPD): what are the function and mechanism of action of SFTPB in COPD? What is the main finding and its importance? Under stimulation of the risk factors of COPD, SFTPB expression is decreased, which may be involved in the formation of COPD. The progress of COPD induces an inflammatory response and reduces SFTPB expression. Levels of prostaglandin-endoperoxide synthase-2 (PTGS2) and inflammatory responses are changed by SFTPB, which indicates that SFTPB promotes the progression of COPD by PTGS2 and inflammation.
Pulmonary surfactant-associated protein B (SFTPB) is a critical protein for lung homeostasis, and polymorphism of its gene is associated with chronic obstructive pulmonary disease (COPD). However, few studies have so far confirmed the functional involvement of SFTPB in COPD. Serum SFTPB and inflammatory cytokine levels were measured in 54 patients with acute exacerbation of COPD and 29 healthy controls. A549 cells were induced using 10% cigarette smoke extract (CSE) and treated with dexamethasone to investigate the effect of inflammation on SFTPB expression, and the effect of SFTPB overexpression and silencing on inflammatory cytokines was measured using real-time PCR and enzyme-linked immunosorbent assay. SFTPB expression was assessed in mouse lung tissues using immunofluorescence. Serum levels of SFTPB were significantly lower in COPD patients than in controls (P = 0.009). Conversely, levels of interleukin (IL)-6 and prostaglandin-endoperoxide synthase-2 (PTGS2) were increased in COPD patients (IL-6: P = 0.006; PTGS2: P = 0.043). After CSE treatment, SFTPB mRNA and protein levels were significantly decreased compared to controls (mRNA: P = 0.002; protein: P = 0.011), while IL-6, IL-8 and PTGS2 were elevated. Dexamethasone treatment increased SFTPB levels. Following overexpression of SFTPB in A549 cells, mRNA and protein levels of IL-6, IL-8 and PTGS2 were significantly reduced, while gene silencing induced the opposite effect. SFTPB levels were significantly reduced in the lung tissue of a mouse model of COPD compared to controls. Reduced SFTPB levels may induce PTGS2 and inflammatory responses in COPD and SFTPB could be a key protein for evaluation of COPD progression.
本研究的核心问题是什么？据报道，肺表面活性物质相关蛋白B（SFTPB）基因多态性与慢性阻塞性肺疾病（COPD）相关：SFTPB在COPD中的功能及作用机制是什么？主要发现及其重要性是什么？在COPD危险因素刺激下，SFTPB表达降低，这可能参与了COPD的形成。COPD的进展诱导炎症反应并降低SFTPB表达。SFTPB改变前列腺素内过氧化物合酶2（PTGS2）水平和炎症反应，这表明SFTPB通过PTGS2和炎症促进COPD的进展。
肺表面活性物质相关蛋白B（SFTPB）是维持肺稳态的关键蛋白，其基因多态性与慢性阻塞性肺疾病（COPD）相关。然而，迄今为止，很少有研究证实SFTPB在COPD中的功能作用。检测了54例COPD急性加重期患者和29例健康对照者的血清SFTPB和炎性细胞因子水平。用10%香烟烟雾提取物（CSE）诱导A549细胞并用地塞米松处理，以研究炎症对SFTPB表达的影响，并用实时PCR和酶联免疫吸附测定法检测SFTPB过表达和沉默对炎性细胞因子的影响。用免疫荧光法评估小鼠肺组织中SFTPB的表达。COPD患者血清SFTPB水平显著低于对照组（P = 0.009）。相反，COPD患者白细胞介素（IL）-6和前列腺素内过氧化物合酶2（PTGS2）水平升高（IL-6：P = 0.006；PTGS2：P = 0.043）。CSE处理后，与对照组相比，SFTPB mRNA和蛋白水平显著降低（mRNA：P = 0.002；蛋白：P = 0.011），而IL-6、IL-8和PTGS2升高。地塞米松处理增加了SFTPB水平。在A549细胞中过表达SFTPB后，IL-6、IL-8和PTGS2的mRNA和蛋白水平显著降低，而基因沉默则产生相反的效果。与对照组相比，COPD小鼠模型肺组织中SFTPB水平显著降低。SFTPB水平降低可能在COPD中诱导PTGS2和炎症反应，SFTPB可能是评估COPD进展的关键蛋白。
