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干扰素-γ对HLA-DR基因的调控。转录及转录后调控。

Regulation of HLA-DR gene by IFN-gamma. Transcriptional and post-transcriptional control.

作者信息

Rosa F M, Fellous M

机构信息

Immunogénétique Humaine, Institut National de la Santé et de la Recherche Médicale U.276, Paris, France.

出版信息

J Immunol. 1988 Mar 1;140(5):1660-4.

PMID:3126233
Abstract

IFN-gamma increases the synthesis and level of mRNA of the HLA class I and II genes, in human cells such as melanomas which normally express both classes of molecules. It also induces the surface expression and mRNA synthesis of HLA-DR genes on cells which normally do not express HLA class II genes such as skin fibroblasts. We have investigated the mechanism by which IFN-gamma increases mRNA levels for class II MHC antigens in human cells. For this purpose, we have studied the effect of IFN-gamma on HLA-DR-alpha transcription rate in two different human cell types: VAL melanoma and JDA2 skin fibroblasts. HLA-DR-alpha mRNA is spontaneously produced in VAL cells and its level is enhanced upon IFN-gamma treatment. We demonstrate here that IFN-gamma increases the transcription of HLA-DR-alpha gene in this cell line. However, the discrepancy observed between HLA-DR-alpha mRNA and transcriptional rates led us to postulate that IFN-gamma also regulates the HLA-DR-alpha gene post-transcriptionally. In the course of these experiments, we found also that human skin fibroblasts, which do not contain detectable amounts of HLA-DR-alpha mRNA, spontaneously transcribe the HLA-DR-alpha gene.

摘要

γ干扰素可增加人类细胞(如通常同时表达两类分子的黑色素瘤细胞)中HLAⅠ类和Ⅱ类基因的mRNA合成及水平。它还能诱导通常不表达HLAⅡ类基因的细胞(如皮肤成纤维细胞)表面表达HLA-DR基因并合成其mRNA。我们研究了γ干扰素增加人类细胞中Ⅱ类MHC抗原mRNA水平的机制。为此,我们研究了γ干扰素对两种不同人类细胞类型(VAL黑色素瘤细胞和JDA2皮肤成纤维细胞)中HLA-DR-α转录速率的影响。VAL细胞可自发产生HLA-DR-α mRNA,γ干扰素处理后其水平会升高。我们在此证明,γ干扰素可增加该细胞系中HLA-DR-α基因的转录。然而,HLA-DR-α mRNA与转录速率之间存在差异,这使我们推测γ干扰素也在转录后水平调控HLA-DR-α基因。在这些实验过程中,我们还发现,不含可检测量HLA-DR-α mRNA的人类皮肤成纤维细胞可自发转录HLA-DR-α基因。

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