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白细胞介素-2(IL-2)和干扰素γ对人单核细胞中IL-2受体γ链基因表达的调控

Regulation by interleukin-2 (IL-2) and interferon gamma of IL-2 receptor gamma chain gene expression in human monocytes.

作者信息

Bosco M C, Espinoza-Delgado I, Schwabe M, Gusella G L, Longo D L, Sugamura K, Varesio L

机构信息

Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center 21702-1201.

出版信息

Blood. 1994 May 15;83(10):2995-3002.

PMID:8180396
Abstract

The interleukin-2 receptor gamma chain (IL-2R gamma) gene codes for a subunit of the IL-2R and is expressed in human lymphoid cells. The present study was undertaken to determine whether human monocytes expressed the IL-2R gamma gene constitutively or after activation by IL-2 or interferon gamma (IFN gamma). Fresh human monocytes constitutively expressed low but significant levels of IL-2R gamma mRNA, and nuclear run-on experiments showed that IL-2R gamma gene was transcriptionally active. Stimulation with IL-2 or IFN gamma induced a major increase of IL-2R gamma mRNA in a time- and a dose-dependent manner. However, neither cytokine increased the transcriptional activity of the gene. The enhancement of IL-2R gamma mRNA expression by either IL-2 or IFN gamma was concomitant with the stabilization of the mRNA, suggesting a postranscriptional level of control. Finally, the augmented expression of IL-2R gamma in IL-2- and IFN gamma-treated monocytes was associated with an increased IL-2-binding activity, compared with that of unstimulated cells. These results provide the first evidence of the expression of the IL-2R gamma gene in nonlymphoid cells and of its modulation by IL-2 and IFN gamma through posttranscriptional mechanisms.

摘要

白细胞介素-2受体γ链(IL-2Rγ)基因编码IL-2R的一个亚基,在人淋巴细胞中表达。本研究旨在确定人单核细胞是组成性表达IL-2Rγ基因,还是在白细胞介素-2(IL-2)或干扰素γ(IFNγ)激活后表达该基因。新鲜人单核细胞组成性表达低水平但显著的IL-2Rγ mRNA,核转录实验表明IL-2Rγ基因具有转录活性。用IL-2或IFNγ刺激可使IL-2Rγ mRNA以时间和剂量依赖性方式大幅增加。然而,这两种细胞因子均未增加该基因的转录活性。IL-2或IFNγ对IL-2Rγ mRNA表达的增强与mRNA的稳定性增加同时出现,提示存在转录后水平的调控。最后,与未刺激细胞相比,经IL-2和IFNγ处理的单核细胞中IL-2Rγ表达的增加与IL-2结合活性的增加相关。这些结果首次证明了IL-2Rγ基因在非淋巴细胞中的表达,以及IL-2和IFNγ通过转录后机制对其进行的调节。

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