Institute of Immunology, CRP-Santé/National Public Health Laboratory, 20A rue Auguste Lumiére, Luxembourg, Grand Duchy of Luxembourg.
Innate Immun. 2011 Feb;17(3):302-20. doi: 10.1177/1753425910369269. Epub 2010 May 25.
The effects of cortisol (CORT) on resting and lipopolysaccharide (LPS)-activated monocyte-derived THP-1 macrophages were investigated by proteomics. Forty-seven proteins were found to be modulated, 20 by CORT, 11 by LPS, and 16 by CORT and LPS. Cortisol-sensitive chaperones and cytoskeletal proteins were mostly repressed. HCLS1, MGN, and MX1 were new proteins identified to be under the transcriptional control of this steroid and new CORT-sensitive variants of MX1, SYWC and IFIT3 were found. FKBP51, a known CORT target gene, showed the strongest response to CORT and synergism with LPS. In resting THP-1 macrophages, 18 proteins were modulated by CORT, with 15 being down-regulated. Activation of macrophages by LPS was associated with enhanced expression of immune response and metabolic proteins. In activated macrophages, CORT had a more equilibrated effect and almost all metabolism-related proteins were up-regulated, whereas immune response proteins were mostly down-regulated. The majority of the LPS up-regulated immune response-related proteins are known interferon (IFN) target genes (IFIT3, MX1, SYWC, PSME2) suggesting activation of the IRF3 signaling pathway. They were all suppressed by CORT. This is the first proteomics study to investigate the effects of CORT on activated immune cells.
采用蛋白质组学方法研究了皮质醇（CORT）对静止和脂多糖（LPS）激活的单核细胞衍生 THP-1 巨噬细胞的影响。发现有 47 种蛋白质受到调节，其中 20 种受 CORT 调节，11 种受 LPS 调节，16 种受 CORT 和 LPS 共同调节。皮质醇敏感的伴侣蛋白和细胞骨架蛋白大多受到抑制。HCLS1、MGN 和 MX1 是新发现的受这种类固醇转录调控的蛋白质，并且发现了新的 CORT 敏感型 MX1、SYWC 和 IFIT3 变体。FKBP51 是一种已知的 CORT 靶基因，对 CORT 的反应最强，并与 LPS 具有协同作用。在静止的 THP-1 巨噬细胞中，有 18 种蛋白质受 CORT 调节，其中 15 种下调。LPS 激活巨噬细胞与免疫反应和代谢蛋白的表达增强有关。在激活的巨噬细胞中，CORT 的作用更加平衡，几乎所有与代谢相关的蛋白质都上调，而免疫反应相关的蛋白质大多下调。大多数 LPS 上调的免疫反应相关蛋白是已知的干扰素（IFN）靶基因（IFIT3、MX1、SYWC、PSME2），提示 IRF3 信号通路的激活。它们都被 CORT 抑制。这是首次研究 CORT 对激活免疫细胞影响的蛋白质组学研究。
