Opposing cytokine-specific effects of all trans-retinoic acid on the activation and expression of signal transducer and activator of transcription (STAT)-1 in THP-1 cells
Opposing cytokine-specific effects of all trans-retinoic acid on the activation and expression of signal transducer and activator of transcription (STAT)-1 in THP-1 cells
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DOI：
10.1046/j.1365-2567.2002.01485.x
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发表时间：
2002-10-01
期刊：
影响因子：
6.4
通讯作者：
Ross, AC
中科院分区：
文献类型：
--
作者：
Chen, QY;Ma, YF;Ross, AC
研究细胞因子和全反式维甲酸(RA)对THP-1单核细胞信号转导和转录激活因子-1(STAT-1)的调节作用。RA(10(-8)M)单独作用不改变THP-1细胞中STAT-1的活化或表达，而RA可增强或延长由干扰素-β或干扰素-γ诱导的STAT-1的激活(酪氨酸701磷酸化)和基因表达(mRNA和蛋白质)。然而，与之相反，RA使脂多糖和/或肿瘤坏死因子-α诱导的STAT-1激活和基因表达减少约50%-70%，并在体外降低了STAT-1共识元件和核因子kappaB(NFkappaB)结合元件的DNA结合活性。这些结果表明，RA可以显著地重新平衡STAT-1依赖的反应，其机制之一可能是通过抑制NFkappaB途径。
The regulation of signal transducer and activator of transcription-1 (STAT-1) by cytokines and all-trans -retinoic acid (RA) was investigated in THP-1 monocytic cells cultured with RA and stimulated with lipopolysaccharide (LPS), tumour necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), and IFN-gamma, individually or in combinations. While RA (10(-8) m) alone did not alter STAT-1 activation or expression in THP-1 cells, RA enhanced or prolonged STAT-1 activation (tyrosine 701 phosphorylation) and gene expression (mRNA and protein) induced by either IFN-beta or IFN-gamma. However, in contrast, RA reduced STAT-1 activation and gene expression induced by LPS and/or TNF-alpha by about 50-70%, and lowered in vitro DNA binding activity to both a STAT-1 consensus element and a nuclear factor kappa B (NFkappaB) binding element. These results imply that RA can significantly rebalance STAT-1-dependent responses, and that one of the mechanisms may be through the inhibition of the NFkappaB pathway.