Transcription profiling of human endothelial and fibroblast cells isolated from umbilical cord veins treated with interferons to identify genes regulated by interferons
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ABSTRACT: IFNs are highly pleiotropic cytokines also endowed with marked anti-angiogenic activity. In this study, the mRNA expression profiles of endothelial cells (EC) exposed in vitro to IFN-alpha, IFN-beta, or; IFN-gamma were determined. We found that in HUVEC as well as in other EC types 175 genes were upregulated (>2-fold increase) by IFNs, including genes involved in the host response to RNA viruses, inflammation, and apoptosis. Interestingly, 41 genes showed a >5-fold higher induction by IFN-alpha in EC compared to human fibroblasts; among them, the gene encoding the angiostatic chemokine CXCL11 was selectively induced by IFN-alpha in EC along with other genes associated; with angiogenesis regulation, including CXCL10, TRAIL, and guanylate binding protein 1 (GBP-1). These transcriptional changes were confirmed and extended by quantitative PCR analysis and ELISA; whereas IFN-alpha and IFN-beta exerted virtually identical effects on transcriptome modulation, a differential gene regulation by type I and type II IFN emerged, especially as far as quantitative aspects were concerned. In vivo, IFN-alpha-producing tumors over-expressed murine CXCL10-11,; GBP-1 and TRAIL, with evidence of CXCL11 production by tumor-associated EC. Overall, these findings improve our understanding of the anti-angiogenic effects of IFNs by showing that these cytokines trigger an anti-angiogenic transcriptional program in EC. Moreover, we suggest that quantitative differences in the magnitude of the transcriptional activation of IFNresponsive genes could form the basis for cell-specific transcriptional signatures. In press, J. Immunol. 2007. Experiment Overall Design: comparison of interferon effects on endothelial cells (HUVEC, HMVEC) and fibrobloasts
ORGANISM(S): Homo sapiens
SUBMITTER: Ulrich Pfeffer
PROVIDER: E-GEOD-3920 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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