IL-7 differentially modulates the expression of IFN-gamma and IL-4 in activated human T lymphocytes by transcriptional and post-transcriptional mechanisms.
IL-7 differentially modulates the expression of IFN-gamma and IL-4 in activated human T lymphocytes by transcriptional and post-transcriptional mechanisms.
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IL-7 通过转录和转录后机制差异调节激活的人 T 淋巴细胞中 IFN-γ 和 IL-4 的表达。
DOI：
10.4049/jimmunol.156.4.1333
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发表时间：
1996
影响因子：
4.4
通讯作者：
P. Moore
中科院分区：
文献类型：
--
作者：
N. Fusaki;Hirofumi Nishixumi;H. Umemori;M. Catharien;Hilkens;J. Grogan;H. J. Mettes;G. Tavana;G. Trinchieri;K. Chinn;P. Moore
我们研究了IL-7在人T淋巴细胞中对ifn - γ和IL-4表达的作用。单独IL-7不能诱导ifn - γ或IL-4 mRNA。然而，IL-7剂量依赖性上调抗cd3或抗cd3 /抗cd28诱导的ifn - γ和IL-4 mRNA表达。在最佳浓度下，IL-7 （5 ng/ml）增加了ifn - γ（8倍）和IL-4（2.5倍）mrna的积累，抗il -12处理不能阻断这种积累。在3 ~ 6小时内观察到ifn - γ mRNA积累增强，而不改变动力学模式。然而，更长的暴露时间（> 12小时）并没有导致抗cd3 /抗cd28与抗cd3 /抗cd28 + il -7刺激的T淋巴细胞的ifn - γ表达不同。mRNA稳定性研究表明，IL-7稳定ifn - γ和IL-4 mRNA转录本：在抗cd3 /抗cd28刺激的T细胞中稳定40和60分钟，而在抗cd3 /抗cd28 + IL-7共刺激的T细胞中稳定120和90分钟。核运行试验显示，在IL-7存在的情况下，ifn - γ基因的转录率增加了大约两倍，而不影响IL-4基因的转录率。与IL-4基因表达相反，环己亚胺处理不能抑制il -7介导的ifn - γ上调。然而，IL-7对ifn - γ和IL-4基因表达的促进作用可被染料木素和环孢素a阻断。最后证明，IL-7对ifn - γ mRNA积累的影响也体现在蛋白水平上。综上所述，这些数据表明IL-7优先上调活化T淋巴细胞中ifn - γ的表达，这是在转录和转录后水平上完成的。
We investigated the role of IL-7 on the expression of IFN-gamma and IL-4 in human T lymphocytes. IL-7 alone did not induce IFN-gamma or IL-4 mRNA. However, IL-7 dose-dependently up-regulates the anti-CD3- or anti-CD3/anti-CD28-induced IFN-gamma and IL-4 mRNA expression. Used at an optimal concentration, IL-7 (5 ng/ml) increased the accumulation of IFN-gamma (eightfold) and IL-4 (2.5-fold) mRNAs, which could not be blocked by anti-IL-12 treatment. The enhanced IFN-gamma mRNA accumulation was observed within 3 to 6 h, without altering the pattern of the kinetics. However, longer exposure (> 12 h) did not result in different IFN-gamma expression for anti-CD3/anti-CD28 vs anti-CD3/anti-CD28 plus IL-7-stimulated T lymphocytes. mRNA stability studies revealed that IL-7 stabilizes both IFN-gamma and IL-4 mRNA transcripts: 40 and 60 min in anti-CD3/anti-CD28-stimulated T cells vs 120 and 90 min in T cells costimulated with anti-CD3/anti-CD28 plus IL-7. Nuclear run-on assays revealed that the transcription rate of the IFN-gamma gene increased approximately twofold in the presence of IL-7, without affecting the transcription rate of the IL-4 gene. The IL-7-mediated IFN-gamma up-regulation could not be inhibited by cycloheximide treatment, in contrast to IL-4 gene expression. However, the promotive effect of IL-7 on IFN-gamma and IL-4 gene expression could be blocked by genistein and cyclosporin A. Finally, it was demonstrated that the effect of IL-7 on IFN-gamma mRNA accumulation was also reflected at the protein level. In summary, these data demonstrate that IL-7 preferentially up-regulates IFN-gamma expression in activated T lymphocytes, which is accomplished at transcriptional and post-transcriptional levels.