Systematic name M6703
Brief description Genes down-regulated in endothelial cells: interferon beta versus IFNG [GeneID=3458].
Full description or 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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 17202376   Authors: Indraccolo S,Pfeffer U,Minuzzo S,Esposito G,Roni V,Mandruzzato S,Ferrari N,Anfosso L,Dell'Eva R,Noonan DM,Chieco-Bianchi L,Albini A,Amadori A
Exact source GSE3920_3486_200_DN
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Source species Homo sapiens
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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