Bileck Andrea, Kreutz Dominique, Muqaku Besnik, Slany Astrid, Gerner Christopher
Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna , Vienna 1090, Austria.
J Proteome Res. 2014 Dec 5;13(12):5989-6000. doi: 10.1021/pr5008625. Epub 2014 Nov 5.
Inflammation is a physiological process involved in many diseases. Monitoring proteins involved in regulatory effects may help to improve our understanding of inflammation. We have analyzed proteome alterations induced in peripheral blood mononuclear cells (PBMCs) upon inflammatory activation in great detail using high-resolution mass spectrometry. Moreover, the activated cells were treated with dexamethasone to investigate their response to this antiphlogistic drug. From a total of 6886 identified proteins, 469 proteins were significantly regulated upon inflammatory activation. Data are available via ProteomeXchange with identifiers PXD001415-23. Most of these proteins were counter-regulated by dexamethasone, with some exceptions concerning members of the interferon-induced protein family. To confirm some of these results, we performed targeted MRM analyses of selected peptides. The inflammation-induced upregulation of proteins such as IL-1β, IL-6, CXCL2, and GROα was confirmed, however, with strong quantitative interindividual differences. Furthermore, the inability of dexamethasone to downregulate inflammation-induced proteins such as PTX3 and TSG6 was clearly demonstrated. In conclusion, the relation of cell function as well as drug-induced modulation thereof was successfully mapped to proteomes, suggesting targeted analysis as a novel and powerful drug evaluation method. Although most consequences of dexamethasone were found to be compatible with the expected mode of action, some unexpected but significant observations may be related to adverse effects.
炎症是许多疾病中涉及的一种生理过程。监测参与调节作用的蛋白质可能有助于增进我们对炎症的理解。我们使用高分辨率质谱法详细分析了炎症激活后外周血单核细胞（PBMC）中诱导的蛋白质组变化。此外，对激活的细胞用 dexamethasone 进行处理，以研究它们对这种抗炎药物的反应。在总共鉴定出的 6886 种蛋白质中，有 469 种蛋白质在炎症激活后受到显著调节。数据可通过 ProteomeXchange 获取，标识符为 PXD001415 - 23。这些蛋白质中的大多数被 dexamethasone 反向调节，但干扰素诱导蛋白家族的成员存在一些例外情况。为了证实其中一些结果，我们对选定的肽段进行了靶向 MRM 分析。炎症诱导的蛋白质如 IL - 1β、IL - 6、CXCL2 和 GROα 的上调得到了证实，然而，个体间存在强烈的定量差异。此外，还清楚地证明了 dexamethasone 无法下调炎症诱导的蛋白质如 PTX3 和 TSG6。总之，细胞功能及其药物诱导的调节关系已成功映射到蛋白质组，表明靶向分析是一种新颖且强大的药物评估方法。尽管发现 dexamethasone 的大多数结果与预期的作用模式相符，但一些意外但显著的观察结果可能与不良反应有关。
