Identification of genes selectively regulated by IFNs in endothelial cells

Stefano Indraccolo, Ulrich Pfeffer, Sonia Minuzzo, Giovanni Esposito, Valeria Roni, Susanna Mandruzzato, Nicoletta Ferrari, Luca Anfosso, Raffaella Dell'Eva, Douglas M. Noonan, Luigi Chieco-Bianchi, Adriana Albini, Alberto Amadori

Research output: Contribution to journalArticlepeer-review


IFNs are highly pleiotropic cytokines also endowed with marked antiangiogenic activity. In this study, the mRNA expression profiles of endothelial cells (EC) exposed in vitro to IFN-α, IFN-β, or IFN-γ were determined. We found that in HUVEC as well as in other EC types 175 genes were up-regulated (>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-α in EC compared with human fibroblasts; among them, the gene encoding the angiostatic chemokine CXCL11 was selectively induced by IFN-α in EC along with other genes associated with angiogenesis regulation, including CXCL10, TRAIL, and guanylate-binding protein 1. These transcriptional changes were confirmed and extended by quantitative PCR analysis and ELISA; whereas IFN-α and IFN-β exerted virtually identical effects on transcriptome modulation, a differential gene regulation by type I and II IFN emerged, especially as far as quantitative aspects were concerned. In vivo, IFN-α-producing tumors overexpressed murine CXCL10 and CXCL11, guanylate-binding protein 1, and TRAIL, with evidence of CXCL11 production by tumor-associated EC. Overall, these findings improve our understanding of the antiangiogenic effects of IFNs by showing that these cytokines trigger an antiangiogenic transcriptional program in EC. Moreover, we suggest that quantitative differences in the magnitude of the transcriptional activation of IFN-responsive genes could form the basis for cell-specific transcriptional signatures.

Original languageEnglish
Pages (from-to)1122-1135
Number of pages14
JournalJournal of Immunology
Issue number2
Publication statusPublished - Jan 15 2007

ASJC Scopus subject areas

  • Immunology


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