REGULATION OF METALLOTHIONEIN GENE-EXPRESSION BY TNF-ALPHA AND IFN-BETA IN HUMAN FIBROBLASTS

被引:25
作者
SCIAVOLINO, PJ
VILCEK, J
机构
[1] NYU, MED CTR, DEPT MICROBIOL, NEW YORK, NY 10016 USA
[2] NYU, MED CTR, KAPLAN CANC CTR, NEW YORK, NY 10016 USA
关键词
INTERFERON; ISRE; METALLOTHIONEIN; TRANSCRIPTION; TUMOR NECROSIS FACTOR;
D O I
10.1006/cyto.1995.0028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have compared the regulation of the human metallothionein (MT)-IIA gene by the cytokines tumour necrosis factor-alpha (TNF) and interferon beta (IFN-beta) in human fibroblasts. Both TNF and IFN-beta induced MT-II mRNA rapidly but stimulation by TNF was more sustained, The effects of TNF and IFN-beta were further distinguished by the action of the protein synthesis inhibitor cycloheximide, which reduced MT-II mRNA stimulation by TNF but enhanced IFN-beta-induced MT-II mRNA, These results suggested that TNF and IFN-beta activate MT-II gene expression by partially distinct mechanisms, Consistent with this notion, combined treatment with both cytokines resulted in more than an additive level of MT-II mRNA induction, TNF and IFN-beta also acted cooperatively in inducing MT-II mRNA in HeLa cells, A reporter construct containing positions -765/+80 of the MT-II promoter linked to the CAT reporter gene failed to respond to either TNF or IFN-beta in HeLa cells, despite the presence of a putative IFN-stimulated response element (ISRE) and an activator protein-1 (AP-1) binding site, suggesting that these elements are insufficient for the activation of the MT-II gene by these cytokines, Thus induction of MT-II expression differs from the genes whose activation by TNF can be induced via the AP-1 element alone, as well as those genes whose activation by IFN is mediated solely through the ISRE site,
引用
收藏
页码:242 / 250
页数:9
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