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
| Autor: | Adrian Whitty, Paula S. Hochman, Alexander V. Lukashin, John Peyman, Margot Brickelmaier, Gerard R. Majeau, Antonio J. da Silva |
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| Rok vydání: | 2002 |
| Předmět: |
Umbilical Veins
DNA Complementary Immunology Gene Expression Antineoplastic Agents Receptor Interferon alpha-beta Interferon alpha-2 Biology Umbilical vein Virology Gene expression Cluster Analysis Humans Receptor Gene Cells Cultured Receptors Interferon Dose-Response Relationship Drug Gene Expression Profiling In vitro toxicology Interferon-alpha Membrane Proteins RNA Interferon-beta Cell Biology GeneCalling Molecular biology Recombinant Proteins Gene expression profiling Genes Interferon Type I Endothelium Vascular Interferon beta-1a Signal Transduction |
| Zdroj: | Journal of Interferon & Cytokine Research. 22:173-188 |
| ISSN: | 1557-7465 1079-9907 |
| DOI: | 10.1089/107999002753536149 |
| Popis: | We analyzed whether interferon-alpha 2b (IFN-alpha 2b) and IFN-beta 1a 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-beta 1a than to IFN-alpha 2b 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-beta 1a were also induced by IFN-alpha 2b and that individual genes were induced to higher levels by IFN-beta 1a. 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-alpha 2b but not by IFN-beta 1a. 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. |
| Databáze: | OpenAIRE |
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