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干扰素调节因子家族蛋白在淋巴细胞中的表达。T细胞活化对Stat-1和干扰素共有序列结合蛋白表达的诱导作用。

Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation.

作者信息

Nelson N, Kanno Y, Hong C, Contursi C, Fujita T, Fowlkes B J, O'Connell E, Hu-Li J, Paul W E, Jankovic D, Sher A F, Coligan J E, Thornton A, Appella E, Yang Y, Ozato K

机构信息

Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.

出版信息

J Immunol. 1996 May 15;156(10):3711-20.

PMID:8621906
Abstract

Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory factor (IRF) family. Evidence indicates that this family has a function in the immune system. Unlike other members of the family, ICSBP is expressed exclusively in the immune system. In this work, immunoblot analysis was performed to study expression of ICSBP and other members of the family in various murine lymphocytes. The results show that all IRF family members are expressed constitutively in B cells throughout development, and in resting and activated cells. In contrast, ICSBP expression was undetectable in thymocytes and resting T cells, while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-gamma) were detected in these cells. Induction of ICSBP (and weakly IRF-1, but not other members) was observed upon activation of T cells following anti-CD3 Ab binding or Con A stimulation. Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells. We show that Stat-1, which binds to the IFN-gamma-responsive element of the ICSBP promoter, was induced following anti-CD3 Ab and Con A stimulation. Stat-1 induction was found in T cells of IFN-gamma+/+, but not of IFN-gamma-/- mice, indicating that T cell activation stimulates the Stat pathway of transcription that is mediated through IFN-gamma. IFN-gamma-activated Stat-1 partly accounted for ICSBP induction in activated T cells, as levels of induction were lower in IFN-gamma-/- than in IFN+/+ T cells. Taken together, these results show that activation of ICSBP is coupled with T cell activation that is partly due to IFN-gamma-induced Stat-1.

摘要

干扰素共有序列结合蛋白(ICSBP)是干扰素调节因子(IRF)家族的一种转录因子。有证据表明该家族在免疫系统中发挥作用。与该家族的其他成员不同,ICSBP仅在免疫系统中表达。在这项研究中,进行了免疫印迹分析以研究ICSBP和该家族其他成员在各种小鼠淋巴细胞中的表达。结果表明,所有IRF家族成员在B细胞发育的整个过程中以及静息和活化细胞中均组成性表达。相比之下,在胸腺细胞和静息T细胞中未检测到ICSBP的表达,而在这些细胞中检测到了所有其他测试的IRF蛋白(IRF-1、IRF-2和ISGF3-γ)。在抗CD3抗体结合或刀豆蛋白A刺激后T细胞活化时,观察到ICSBP(以及弱诱导的IRF-1,但不是其他成员)的诱导。一旦T细胞被激活,ICSBP在Th1和Th2细胞中均稳定表达。我们发现,与ICSBP启动子的IFN-γ反应元件结合的Stat-1在抗CD3抗体和刀豆蛋白A刺激后被诱导。在IFN-γ+/+小鼠的T细胞中发现了Stat-1的诱导,但在IFN-γ-/-小鼠的T细胞中未发现,这表明T细胞活化刺激了通过IFN-γ介导的Stat转录途径。IFN-γ激活的Stat-1部分解释了活化T细胞中ICSBP的诱导,因为在IFN-γ-/- T细胞中的诱导水平低于IFN+/+ T细胞。综上所述,这些结果表明ICSBP的激活与T细胞激活相关,这部分归因于IFN-γ诱导的Stat-1。

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