Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae
Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae
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DOI：
10.1038/sj.bjp.0705500
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发表时间：
2003-11-01
影响因子：
7.3
通讯作者：
Tsai, WJ
中科院分区：
文献类型：
--
作者：
Kuo, YC;Weng, SC;Tsai, WJ
1研究蝉花麦角甾醇过氧化物（C28 H44 O3; Cpd 6A）对植物血凝素（PHA）刺激的人T细胞增殖的影响。2结果表明，Cpd 6A抑制PHA刺激的T细胞增殖约24 h。细胞周期分析表明，化合物6A阻止了活化T细胞从G1期过渡到S期的细胞周期进程。3为了定位细胞周期中发生停滞的点，需要一系列导致G1/S边界的关键调节事件，包括细胞周期蛋白D2、E、A1和B1、白细胞介素（IL）-2、IL-4、干扰素-γ的表达4化合物6A以剂量依赖性方式抑制活化的T淋巴细胞中细胞周期蛋白E、IL-2、IL-4、IL-10和IFN-γ的产生和mRNA表达。5 AP-1蛋白的表达，包括c-Fos和c-Jun，Cpd 6A可降低活化T淋巴细胞的增殖。动力学研究表明，化合物6A抑制T细胞IL-2 mRNA表达的作用可能与抑制c-Fos蛋白合成有关。化合物6A处理后的T细胞增殖通过加入IL-2、IL-4和IFN-γ而部分恢复。化合物6A对PHA激活的T细胞增殖的这些抑制作用似乎至少部分通过抑制早期基因转录物，特别是细胞周期蛋白E、IFN-γ、IL-2和IL-4的转录物，以及通过阻止细胞中的细胞周期进程来介导。
1 Effects of ergosterol peroxide (C28H44O3; Cpd 6A) from Cordyceps cicadae on phytohemagglutinin (PHA)-stimulated cell proliferation were studied in primary human T cells.2 The results showed that Cpd 6A suppressed T-cell proliferation for about 24 h after stimulation with PHA. Cell cycle analysis indicated that Cpd 6A arrested the cell cycle progression of activated T cells from the G1 transition to the S phase.3 To localize the point in the cell cycle where arrest occurred, a set of key regulatory events leading to the G1/S boundary, including the expression of cyclins D2, E, A1, and B1, interleukin (IL)-2, IL-4, interferon-gamma (IFN-gamma), and activating protein-1 (AP-1), was examined.4 Cpd 6A suppressed, in activated T lymphocytes, the production and mRNA expression of cyclin E, IL-2, IL-4, IL-10, and IFN-gamma in a dose-dependent manner.5 Expression of AP-1 proteins, consisting of c-Fos and c-Jun, in activated T lymphocytes was decreased by Cpd 6A. The kinetic study indicated that the inhibitory effects of Cpd 6A on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. T-cell proliferation after Cpd 6A treatment was partially restored by addition of IL-2, IL-4, and IFN-gamma.6 These suppressant effects of Cpd 6A on T-cell proliferation, activated by PHA, appeared to be mediated, at least in part, through the inhibition of early gene transcripts, especially those of cyclin E, IFN-gamma, IL-2, and IL-4, and by arresting cell cycle progression in the cells.