ENHANCED INTERLEUKIN-1 PRODUCTION BY HUMAN MONOCYTE CELL-LINES FOLLOWING TREATMENT WITH 5-AZACYTIDINE
ENHANCED INTERLEUKIN-1 PRODUCTION BY HUMAN MONOCYTE CELL-LINES FOLLOWING TREATMENT WITH 5-AZACYTIDINE
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DOI：
10.1002/jlb.41.1.40
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发表时间：
1987-01-01
影响因子：
5.5
通讯作者：
YOUNG, HA
中科院分区：
文献类型：
--
作者：
KOVACS, EJ;OPPENHEIM, JJ;YOUNG, HA
最近的研究表明，DNA修饰，如特定碱基的甲基化或改变碱基的取代，可以在真核基因表达的控制中发挥重要作用。我们选择检测两种DNA修饰剂，5-氮杂胞苷（AZA）和5-溴脱氧尿苷（BUdR），对人单核细胞系THP-1和U937.1中白细胞介素-1（IL-1）基因表达的影响。THP-1在用脂多糖（LPS）刺激时产生IL-1，而U937.1不产生。用AZA处理后，可以诱导U937.1细胞产生IL-1 β。mRNA并释放IL-1，但只有在刺激如LPS存在时。此外，IL-1 β的水平也随时间而变化。诱导后的THP-1细胞经AZA处理后，其mRNA的产生和IL-1的释放均增加一倍。与此相反，我们不能改变IL-1的生产与BUdR在诱导剂的存在或不存在的情况下处理的细胞。这些结果表明，IL-1的产生可能是，在一定程度上，由DNA甲基化调节。
Recent studies suggest that DNA modification, such as methylation of specific bases or substitution of altered bases, can play an important role in the control of eukaryotic gene expression. We chose to examine the effects of two DNA modifying agents, 5-azacytidine (AZA) and 5-bromodeoxyuridine (BUdR), on interleukin-1 (IL-1) gene expression in the human monocyte cell lines THP-1 and U937.1. THP-1 produced IL-1 upon stimulation with lipopolysaccharide (LPS), whereas U937.1 did not. Following treatment with AZA, U937.1 cells could be induced to produce IL-1 .beta. mRNA and release IL-1, but only if a stimulus such as LPS was present. In addition, the level of IL-1 .beta. mRNA produced and IL-1 released by THP-1 cells after induction could be doubled by treatment with AZA. In contrast, we were unable to alter IL-1 production by treatment of cells with BUdR in the absence or presence of inducers. These results suggest that the production of IL-1 may be, in part, regulated by methylation of DNA.