INDUCTION OF TYPE-I INTERFERON GENES AND INTERFERON-INDUCIBLE GENES IN EMBRYONAL STEM-CELLS DEVOID OF INTERFERON REGULATORY FACTOR-I

被引:80
作者
RUFFNER, H [1 ]
REIS, LFL [1 ]
NAF, D [1 ]
WEISSMANN, C [1 ]
机构
[1] UNIV ZURICH, INST MOLEK BIOL 1, CH-8093 ZURICH, SWITZERLAND
关键词
GENE DISRUPTION; INTERFERON PROMOTER; GENE REGULATION;
D O I
10.1073/pnas.90.24.11503
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Overexpression of interferon regulatory factor 1 (IRF-1) can induce expression of the interferon (IFN) beta gene, at least in certain cells. A role of IRF-1 in the activation of IFN-alpha genes has also been claimed. We have generated embryonal stem cells in which both IRF-1 alleles were disrupted. In undifferentiated embryonal stem cells, virus-induced levels of IFN-alpha RNA were similar for wild-type and IRF-1%, and there was little induction of IFN-beta RNA in either cell type. In 8-day differentiated cells, the levels of virus-induced IFN-beta RNA, but not of IFN-alpha RNA, were about 10-fold higher than in undifferentiated cells and only slightly higher in wild-type than in IRF-1% cells. Thus, although IRF-1 at high levels may elicit or augment induction of IFN genes under certain circumstances, it is not essential for IFN gene induction by virus. Lack of IRF-1 had no effect on the IFN-induced expression levels of the IFN-inducible genes tested; however, there was little or no constitutive expression of (2'-5')oligoadenylate synthetase in IRF-1% embryonal stem cells, in contrast to wild-type cells.
引用
收藏
页码:11503 / 11507
页数:5
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