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γ干扰素通过转录调控一个与血小板蛋白具有同源性的早期反应基因。

Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins.

作者信息

Luster A D, Unkeless J C, Ravetch J V

出版信息

Nature. 1985;315(6021):672-6. doi: 10.1038/315672a0.

DOI:10.1038/315672a0
PMID:3925348
Abstract

Interferons are a family of proteins first identified by their ability to induce cellular resistance to infection by many viruses. In addition to the antiviral properties it shares with the alpha- and beta-interferons, gamma-interferon (IFN-gamma), a lymphokine secreted by activated T cells, activates macrophages, stimulates B cells, increases fibroblast and endothelial cell resistance to many nonviral intracellular parasites and modulates cell-surface proteins central to immune cell regulation. To identify molecules involved in the IFN-gamma response and characterize their modulation, we have isolated genes that are induced following recombinant IFN-gamma treatment of U937 cells, a histiocytic lymphoma cell line with monocytic characteristics. We report here the molecular cloning and characterization of a gene regulated by rIFN-gamma in U937 cells as well as in human mononuclear cells, fibroblasts and endothelial cells. Messenger RNA from this gene is induced within 30 min of rIFN-gamma treatment and demonstrates maximal (greater than 30-fold) accumulation within 5 h. Increased transcription is partly responsible for this accumulation. This gene encodes a protein of relative molecular mass (Mr) 12,378 which has significant amino-acid homology to platelet factor-4 and beta-thromboglobulin, two chemotatic proteins released by platelets on degranulation. This IFN-gamma-inducible protein may be a member of a family of proteins involved in the inflammatory process.

摘要

干扰素是一类蛋白质,最初因其能诱导细胞对多种病毒感染产生抗性而被发现。γ干扰素(IFN-γ)是活化T细胞分泌的一种淋巴因子,除了具有与α干扰素和β干扰素共有的抗病毒特性外,还能激活巨噬细胞、刺激B细胞、增强成纤维细胞和内皮细胞对许多非病毒细胞内寄生虫的抗性,并调节对免疫细胞调节至关重要的细胞表面蛋白。为了鉴定参与IFN-γ应答的分子并表征其调节作用,我们分离了在用重组IFN-γ处理U937细胞(一种具有单核细胞特征的组织细胞淋巴瘤细胞系)后被诱导的基因。我们在此报告在U937细胞以及人单核细胞、成纤维细胞和内皮细胞中受rIFN-γ调节的一个基因的分子克隆和表征。该基因的信使核糖核酸在rIFN-γ处理后30分钟内被诱导,并在5小时内显示出最大(超过30倍)积累。转录增加是这种积累的部分原因。该基因编码一种相对分子质量(Mr)为12378的蛋白质,它与血小板因子4和β-血小板球蛋白具有显著的氨基酸同源性,这两种趋化蛋白是血小板脱颗粒时释放的。这种IFN-γ诱导蛋白可能是参与炎症过程的蛋白质家族的一员。

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