Cell and type specificity of interferon action. Unusual characteristics of the transcriptional control of gene expression by interferon‐γ in T cells*

Cell and type specificity of interferon action. Unusual characteristics of the transcriptional control of gene expression by interferon‐γ in T cells*
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干扰素作用的细胞和类型特异性。T 细胞中干扰素-γ 基因表达转录控制的异常特征*

DOI:
10.1002/eji.1830200608
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发表时间:
1990
影响因子:
5.4
通讯作者:
S. Landolfo
S. Landolfo
中科院分区:
医学3区
文献类型:
--
作者:
G. Gribaudo;M. Gariglio;G. Cavallo;S. Landolfo

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我们研究了干扰素(IFN)-γ和IFN-α调节小鼠T细胞和其他组织来源的细胞类型中2′-5 ′-寡腺苷酸合成酶(2-5A合成酶)和I类主要组织相容性复合物抗原表达的机制。当用IFN-α处理时,成纤维细胞和T细胞系都显示出2-5A合成酶活性和相应mRNA的显著增加。IFN-α在转录水平诱导T细胞中酶活性的增强,如通过核运行分析所确定的。相比之下,IFN-γ仅能够增加成纤维细胞中的2-5A合成酶活性,而不能增加T细胞中的2-5A合成酶活性。核连续试验表明,T细胞中的2-5A合成酶基因不被IFN-γ转录激活。在IFN-α和-γ处理后,我们还观察到成纤维细胞和T细胞系中I类基因表达的显著增加,如在细胞表面和细胞质RNA积累上所测量的。在T细胞系DO 1110中,观察到的I类转录物稳态水平的增加是H-2基因转录率高的结果,如运行分析所示。然而,IFN-α和IFN-γ之间参与这种IFN-依赖性H-2基因转录激活的分子机制是不同的。当T细胞系DO 1110、L12-R4和EL 4用含有报告基因(氯霉素乙酰转移酶)的质粒转染时,IFN-α能够激活这些构建体的转录,该报告基因在237 bp或1.4 kb的调节性IFN-应答DNA元件的控制下。相比之下,IFN-γ不识别IFN-应答元件,该元件本身在非T细胞来源的其他细胞类型中响应IFN-γ而激活报告基因的转录。因此,在所检测的T细胞系中,IFN-γ通过作用于位于本研究中所用调节片段上游或帽位点下游的DNA元件来增加H-2基因表达。这表明在IFN应答元件的活化中可能存在细胞特异性,这反过来可能以acell特异性方式调节IFN诱导型基因表达。因此,IFN-γ对T细胞的差异生物学活性可以通过转录水平上的差异基因激活来产生。
We have examined the mechanisms by which interferon (IFN)‐γ and IFN‐α regulate the expression of 2′‐5′‐oligoadenylate synthetase (2–5A synthetase) and class I major histocompatibility complex antigens in murine T cells and in cell types of other histological origin. When treated with IFN‐α both fibroblasts and T cell lines displayed a marked increase of the 2–5A synthetase activity and of the corresponding mRNA. The augmentation of the enzyme activityin T cells was induced by IFN‐α at the transcriptional level, as determined by nuclear run‐on analysis. In contrast IFN‐γ was capable of increasing 2–5A synthetase activity only in fibroblasts, but not in T cells. Nuclear run‐on assays revealed that the 2–5A synthetase gene in T cells is not transcriptionally activated by IFN‐γ. After IFN‐α and ‐γ treatment we also observed a significant increase in class I gene expression in fibroblasts and T cell lines as measured both on the cell surface and by cytoplasmic RNA accumulation. In the case of the T cell line, DO1110, the observed increase in the steady‐state levels of class I transcripts was a consequence of a high rate of H‐2 gene transcription as demonstrated by run‐on analysis. However, the molecular mechanisms involved in this IFN‐dependent H‐2 gene transcriptional activation are differentbetween IFN‐α and IFN‐γ. When the T cell lines DO1110, L12‐R4 and EL4 were transfected with a plasmid containing a reporter gene (chloramphenicol acetyltransferase) under the control of a regulatory IFN‐responsive DNA element of 237 bp or 1.4 kb, IFN‐α was able to activate the transcription of these constructs. In contrast, IFN‐γ did not recognize the IFN‐responsive element which, by itself, activated transcription of the reporter gene in response to IFN‐γ in other cellular types of non‐T cell origin. Therefore, in the T cell linesexamined, IFN‐γ increases the H‐2 gene expression by acting on DNA elements located upstream of the regulatory segment used in this study or downstream of thecap site. This suggests a possible cell specificity in the activation of an IFN‐responsive element, that in turn may regulate the IFN‐inducible gene expression in acell‐specific fashion. Thus, the differential biological activities of IFN‐γ on T cells could be generated by a differential gene activation at the transcriptional level.
野生型和变异型小鼠肝癌细胞中 2,3,7,8-四氯二苯并-p-二恶英对细胞色素 P1-450 基因转录的调节。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Israel,DI;WhitlockJr,JP
通讯作者: WhitlockJr,JP
DOI: 10.1073/pnas.84.18.6394
发表时间: 1987-09-01
影响因子: 11.1
作者:
REICH, N;EVANS, B;DARNELL, JE
通讯作者: DARNELL, JE
干扰素对小鼠 I 类基因的调节是由位于转录起始位点 5 和 3 的区域控制的。
DOI: 10.1073/pnas.84.10.3380
发表时间: 1987
影响因子: 11.1
作者:
Korber,B;Hood,L;Stroynowski,I
通讯作者: Stroynowski,I
DOI: --
发表时间: 1979-10
期刊: The Journal of biological chemistry
影响因子: --
作者:
M. Minks;D. West;S. Benvin;C. Baglioni
通讯作者: M. Minks;D. West;S. Benvin;C. Baglioni
鉴定人组织相容性白细胞抗原DRα链基因的干扰素-γ反应区5,该基因在人多形性胶质母细胞瘤系中有活性。
DOI: --
发表时间: 1987
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Basta,PV;Sherman,PA;Ting,JP
通讯作者: Ting,JP