Jurkat细胞
NFAT公司
氧化应激
分子生物学
氧化磷酸化
c-jun公司
信使核糖核酸
转录因子
细胞生物学
化学
报告基因
生物
基因表达
T细胞
基因
生物化学
免疫学
免疫系统
作者
L Beiqing,M Chen,R L Whisler
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:1996-07-01
卷期号:157 (1): 160-169
被引量:57
标识
DOI:10.4049/jimmunol.157.1.160
摘要
Abstract Sublethal levels of oxidative stress are well known to alter T cell functional responses, but the underlying mechanisms are unknown. The current study examined the effects of oxidative stress on transcriptional activities mediated by c-Fos/c-Jun AP-1 and the nuclear factor of activated T cells (NF-AT). The present results show that Jurkat T cells acutely exposed to micromolar concentrations of H2O2 exhibit substantial increases in AP-1 binding activity and the expression of c-jun but not c-fos mRNA. The preferential induction of c-jun by H2O2 did not represent redox stabilization of mRNA transcripts, and oxidative signals closely resembled PHA/PMA stimulation by effectively transactivating the full length c-jun promoter via the proximal jun1 tumor promoter-responsive element (TRE)-like promoter element. Similarly, the complexes binding the consensus AP-1 TRE and jun TRE-like motifs in cells exposed to oxidative signals or PHA/PMA were indistinguishable, being composed of c-Fos, c-Jun, and JunD. However, PHA/PMA but not oxidative signals induced the coordinate activation of reporter constructs containing the AP-1-TRE, NF-AT, and IL-2 promoter regions along with IL-2 mRNA expression. Furthermore, sublethal levels of H2O2 actively suppressed the transcriptional activation of NF-AT and IL-2 reporters as well as the expression of IL-2 mRNA in cells stimulated with PHA/PMA. Gel shift analysis revealed that oxidative suppression of NF-AT represented inhibition in the early generation of NFAT complexes rather than the binding of preformed NF-AT complexes. These results suggest that oxidative signals can positively and negatively regulate T cell transcriptional events and that changes in cellular redox can uncouple AP-1 regulation of c-jun from transcriptional up-regulation of IL-2 via NF-AT.
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