HEAVY-METAL MODULATION OF THE HUMAN INTERCELLULAR-ADHESION MOLECULE (ICAM-1) GENE-EXPRESSION

HEAVY-METAL MODULATION OF THE HUMAN INTERCELLULAR-ADHESION MOLECULE (ICAM-1) GENE-EXPRESSION
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DOI:
10.1016/0167-4781(94)00237-w
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发表时间:
1995-03-14
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子:
--
通讯作者:
GULINO, A
GULINO, A
中科院分区:
其他
文献类型:
--
作者:
MARTINOTTI, S;TONIATO, E;GULINO, A

文献摘要

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细胞间粘附分子1(ICAM-1)可以在许多不同的细胞类型上被一组在炎症过程中释放的各种调节剂(IL 1 β、TNF、LPS、IFN-γ)诱导。我们已经研究了与炎症反应的应激和生物物理扰动相关的其他因素也可能调节ICAM-1的可能性。在这里,我们报告说,重金属,特别是锌,可以增强ICAM-1基因的表达,积极参与炎症过程中的不同水平的细胞。ICAM-1基因表达的动力学研究显示,金属处理后4小时诱导水平最高,随后在12小时内迅速下降至基础水平。对增强的基因表达的影响主要是由于转录速率的快速增加,如核运行实验所示。在B类淋巴母细胞中,而不是在成纤维细胞中,RNA表达的增加似乎明显大于随后的蛋白质表达的增加,这表明ICAM-1的转录后调节的另一个点发生,并且可能与细胞特异性有关。
The intercellular adhesion molecule 1 (ICAM-1) can be induced on many different cell types by a set of various modulators (IL1 beta, TNF, LPS, IFN-gamma), which are released during the inflammatory process. We have investigated the possibility that other factors, related to the stress and biophysical perturbations of the inflammatory response, may also modulate ICAM-1. Here, we report that heavy metals, in particular zinc, can enhance the expression of the ICAM-1 gene on cells actively involved at different levels during inflammation. Kinetic studies of the ICAM-1 gene expression shows a maximum level of induction 4 h after treatment with metals, followed by a rapid decrease to basal levels within 12 h. The effect on enhanced gene expression is mostly due to a rapid increase of the transcriptional rate as shown by nuclear run-on experiments. In B lymphoblastoid cells, but not in fibroblasts, the increase in RNA expression seems significantly greater that the subsequent increase in protein expression, suggesting that a further point of post-transcriptional regulation of ICAM-1 occurs and may be linked to the cellular specificity.