Comparison of gene expression patterns induced by treatment of human umbilical vein endothelial cells with IFN-α2b vs. IFN-β1a:: Understanding the functional relationship between distinct type I interferons that act through a common receptor
Comparison of gene expression patterns induced by treatment of human umbilical vein endothelial cells with IFN-α2b vs. IFN-β1a:: Understanding the functional relationship between distinct type I interferons that act through a common receptor
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DOI：
10.1089/107999002753536149
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发表时间：
2002-02-01
影响因子：
2.3
通讯作者：
Hochman, PS
中科院分区：
文献类型：
--
作者：
da Silva, AJ;Brickelmaier, M;Hochman, PS
我们分析了干扰素-α 2b（IFN-α 2b）和IFN-β 1a是否与它们的共同受体结合，以产生具有不同信号传导特性的活化受体复合物。在体外试验中，人血管内皮细胞（HUVEC）对IFN-β 1 a的敏感性是IFN-α 2b的100-1000倍。一个nonarray-based表达谱（GeneCalling）技术被用来比较这些IFN诱导的基因表达的模式和水平，作为最广泛的手段，通过它可以测量信号事件。为了区分亚型相关差异与剂量相关效应，从用50-5000 pg/ml的每种IFN处理的HUVEC制备RNA。结果表明，在50 pg/ml IFN下，只有一部分由IFN-beta 1a诱导的基因也被IFN-alpha 2b诱导，并且个别基因被IFN-beta 1a诱导至更高水平。相反，在5000 pg/ml时，两种亚型诱导基本相同的基因组达到相似的表达水平。没有基因被观察到被IFN-α 2b唯一诱导，而不是IFN-β 1a。结果表明，这两种IFN本质上能够诱导类似的基因诱导反应，并没有提供证据表明它们产生具有不同信号传导特性的活化受体复合物。相比之下，两种IFN产生的基因诱导模式在亚饱和和潜在的生理上更相关的浓度下在定性和定量上都是不同的。
We analyzed whether interferon-alpha2b (IFN-alpha2b) and IFN-beta1a engage their common receptor to generate activated receptor complexes possessing distinct signaling properties. Human vascular endothelial cells (HUVEC) are 100-1000-fold more sensitive to IFN-beta1a than to IFN-alpha2b in in vitro assays. An nonarray-based expression profiling (GeneCalling) technology was employed to compare the patterns and levels of gene expression induced by these IFN as the broadest means by which signaling events could be measured. To distinguish subtype-related differences from dose-related effects, RNA was prepared from HUVEC treated with 50-5000 pg/ml of each IFN. The results showed that at 50 pg/ml IFN, only a subset of the genes induced by IFN-beta1a were also induced by IFN-alpha2b and that individual genes were induced to higher levels by IFN-beta1a. In contrast, at 5000 pg/ml, both subtypes induced essentially identical sets of genes to similar levels of expression. No genes were seen to be induced uniquely by IFN-alpha2b but not by IFN-beta1a. The results show that the two IFN are intrinsically capable of inducing similar gene induction responses and do not provide evidence that they generate activated receptor complexes possessing distinct signaling properties. In contrast, the two IFN generate gene induction patterns that are both qualitatively and quantitatively distinct at subsaturating and potentially physiologically more relevant concentrations.