Liu Dongdong, Mao Pu, Huang Yongbo, Liu Yiting, Liu Xiaoqing, Pang Xiaoqing, Li Yimin
State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Guangzhou, Guangdong 510120, China ; Intensive Care Unit, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Guangzhou, Guangdong 510120, China ; Infection Control Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Mediators Inflamm. 2014;2014:469358. doi: 10.1155/2014/469358. Epub 2014 Jun 15.
Acute respiratory distress syndrome (ARDS) remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI) lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS) challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.
尽管对急性呼吸窘迫综合征(ARDS)的发病机制进行了数十年的大量研究,但它在重症患者中仍然是一种高发病率和高死亡率的疾病实体。为了获得急性肺损伤(ALI)肺组织中的整体蛋白质表达变化,我们采用了高通量蛋白质组学方法来鉴定可能参与ALI发病机制的关键成分。在本研究中,我们分析了铜绿假单胞菌诱导的ALI大鼠的肺组织蛋白质组,并鉴定出18种蛋白质,其表达水平与正常对照组相比变化超过两倍。特别地,我们发现体外气道上皮细胞经脂多糖(LPS)刺激后,培养基中PRDX1的表达升高。此外,PRDX1的过表达增加了促炎细胞因子白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)的表达,而敲低PRDX1导致LPS诱导的细胞因子表达下调。总之,我们的研究结果揭示了ALI大鼠模型肺组织蛋白质组的整体变化,并表明PRDX1可能通过促进炎症反应在ARDS的发病机制中起关键作用,为开发针对ALI的新疗法提供了一种新策略。