Zhongshan Hospital Institute of Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Medical College, Fudan University, Shanghai, China.
Cell Biol Toxicol. 2018 Apr;34(2):109-123. doi: 10.1007/s10565-017-9405-x. Epub 2017 Aug 4.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as a serious event has high mortality and medical costs. Systemic inflammation and immune response are the major factors influencing the outcome and quality of patient with AECOPD. On basis of identification and validation of AECOPD-specific inflammatory biomarkers, the present study aimed to identify AECOPD-specific immunomodulatory mediators by evaluating dynamic genomic and proteomic profiles of peripheral blood mononuclear cells (PBMCs) and plasma in patients with AECOPD on day 1, 3, and 10 after the hospital admission, to compare with healthy controls or patients with stable COPD. We found that genes and proteins of C1QC and C1RL were co-differentially up-expressed in patients with COPD or AECOPD, while haptoglobin (HP), ORM1, SERPING1, and C3 were identified as a panel of AECOPD-specific immunomodulatory mediators. We also found that inflammatory stimuli could up-regulate osteopontin (OPN)-associated HP expression through the PI3K signal pathway in A549 cells. Block of autocrine production of OPN by gene inhibition could reduce HP production from inflammation-induced lung epithelial cells. The complex network of AECOPD- or COPD-specific immunomodulatory mediators will benefit the development of precision or personalized medicine strategies for prevention and treatment of AECOPD.
慢性阻塞性肺疾病（COPD）急性加重（AECOPD）是一种严重的疾病，其死亡率和医疗费用都很高。全身炎症和免疫反应是影响 AECOPD 患者预后和生活质量的主要因素。本研究在鉴定和验证 AECOPD 特异性炎症生物标志物的基础上，通过评估 AECOPD 患者入院后第 1、3、10 天外周血单个核细胞（PBMC）和血浆的动态基因组和蛋白质组谱，与健康对照组或稳定 COPD 患者进行比较，旨在寻找 AECOPD 特异性免疫调节介质。结果发现，C1QC 和 C1RL 的基因和蛋白在 COPD 或 AECOPD 患者中共同呈差异性高表达，而结合珠蛋白（HP）、ORM1、SERPING1 和 C3 则被鉴定为 AECOPD 特异性免疫调节介质的一个组合。我们还发现，炎症刺激物可以通过 PI3K 信号通路上调 A549 细胞中与骨桥蛋白（OPN）相关的 HP 表达。通过基因抑制阻断自分泌产生的 OPN 可以减少炎症诱导的肺上皮细胞中 HP 的产生。AECOPD 或 COPD 特异性免疫调节介质的复杂网络将有助于开发预防和治疗 AECOPD 的精准或个性化医学策略。
