Suppression of cytochrome P450IA1 by interleukin-6 in human HepG2 hepatoma cells.
Suppression of cytochrome P450IA1 by interleukin-6 in human HepG2 hepatoma cells.
复制标题
在人 HepG2 肝癌细胞中白细胞介素 6 对细胞色素 P450IA1 的抑制。
DOI：
10.1016/0006-2952(94)90391-3
复制
发表时间：
1994
影响因子：
5.8
通讯作者：
Sassa,S
中科院分区：
文献类型：
--
作者：
Fukuda,Y;Sassa,S
以人肝癌细胞株HepG2为研究对象，观察了急性时相反应的主要诱导物--白介素6(IL-6)对细胞色素P450IA1(CYPIA1)表达的影响。IL-6可降低3-甲基胆蒽诱导的CyPIA1蛋白及其mRNA水平。核径流分析表明，IL-6的作用主要是转录作用。IL-6作用于HepG2细胞后，使血红素分解代谢的限速酶--微粒体血红素加氧酶的mRNA表达增加，提示IL-6抑制细胞色素PIA1基因的表达可能是由于丢失了血红素。与这一假设一致的是，与血红素加氧酶抑制剂锡中卟啉同时处理细胞，阻止了IL-6介导的对细胞色素PIA1的抑制。这些发现表明，IL-6对P450IA1mRNA的抑制似乎至少部分发生在血红素加氧酶诱导的游离血红素含量的下降。我们的结果提出了这样一种可能性，即影响细胞内血红素浓度的其他生理和环境刺激也可能调节P450的表达。
The effects of interleukin-6 (IL-6), the major inducer of the acute-phase reaction, on the expression of cytochrome P450IA1 (CYPIA1) were examined using human HepG2 hepatoma cells. Treatment of cells with IL-6 decreased the level of 3-methylhcholanthrene-induced CYPIA1 protein and its mRNA. Nuclear runoff analysis revealed that the effect of IL-6 was largely transcriptional. IL-6 treatment of HepG2 cells increased mRNA for microsomal heme oxygenase, the rate-limiting enzyme in heme.catabolism, suggesting that the suppressive effect of IL-6 on CYPIA1 mRNA may be due to a loss of heme. Consistent with this hypothesis, simultaneous treatment of cells with Sn-mesoporphyrin, an inhibitor of heme oxygenase, prevented the IL-6-mediated suppression of CYPIA1. These findings suggest that the suppression of P450IA1 mRNA by IL-6 appears to occur, at least in part, from the decline in free heme content as a result of the induction of heme oxygenase. Our results raise the possibility that other physiological as well as environmental stimuli which affect cellular heme concentrations may also modulate the expression of P450s.