Comparison of Gene Expression Patterns Induced by Treatment of Human Umbilical Vein Endothelial Cells with IFN- α 2b vs. IFN- β 1a: Understanding the Functional Relationship Between Distinct Type I Interferons That Act Through a Common Receptor

Abstract

We analyzed whether interferon-α2b (IFN-α2b) and IFN-β1a 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-β1a than to IFN-α2b 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-β1a were also induced by IFN-α2b and that individual genes were induced to higher levels by IFN-β1a. 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-α2b but not by IFN-β1a. 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.