ACTIVITY OF STAT FAMILY TRANSCRIPTION FACTORS IS DEVELOPMENTALLY CONTROLLED IN CELLS OF THE MACROPHAGE LINEAGE

被引:11
作者
EILERS, A [1 ]
DECKER, T [1 ]
机构
[1] VIENNA BIOCTR,INST MICROBIOL & GENET,A-1030 VIENNA,AUSTRIA
关键词
D O I
10.1016/S0171-2985(11)80562-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Stat family transcription factors are activated in response to a variety of cytokines to bind to a class of DNA elements termed gamma interferon activation site (GAS)-like elements. Here we investigate two GAS-binding transcription factors, the gamma-interferon activation factor (GAF) and the differentiation-induced factor (DIF) that are activated by interferon-gamma (IFN-gamma) in U937 cells. Treatment of U937 cells with phorbol ester (TPA) induces differentiation from a promonocyte into a monocyte stage of macrophage devlopment. Mnocytic differentiation led to an increased transcriptional response of GAS-containing genes to IFN-gamma. TPA treatment also caused a profound change in the IFN-gamma activation of GAF and DIF. GAF DNA-binding activity was activated much better in the monocyte stage and the GAF constituent Stat 1 showed increased phosphorylation. In contrast, DIF activation by IFN-gamma was found in promonocytes but was virtually absent in monocytes. Moreover, DIF activation was observed during TPA-induced monocytic differentiation and after treatment of macrophages with the macrophage differentiation factor CSF-1. Our data suggest DIF to be part of a developmental program leading to terminal macrophage differentiation and GAF to be a transcription factor bringing about the stronger activation response of mature macrophages to IFN-gamma.
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页码:328 / 333
页数:6
相关论文
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