Identification of IRF-8 and IRF-1 target genes in activated macrophages

Natalie Dror, Michal Alter-Koltunoff, Aviva Azriel, Ninette Amariglio, Jasmine Jacob-Hirsch, Sharon Zeligson, Avigail Morgenstern, Tomohiko Tamura, Hansjörg Hauser, Gideon Rechavi, Keiko Ozato, Ben Zion Levi

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon regulatory factor 1 (IRF-1) and IRF-8, also known as interferon consensus sequence binding protein (ICSBP), are important regulators of macrophage differentiation and function. These factors exert their activities through the formation of heterocomplexes. As such, they are coactivators of various interferon-inducible genes in macrophages. To gain better insights into the involvement of these two transcription factors in the onset of the innate immune response and to identify their regulatory network in activated macrophages, DNA microarray was employed. Changes in the expression profile were analyzed in peritoneal macrophages from wild type mice and compared to IRF-1 and IRF-8 null mice, before and following 4 h exposure to IFN-γ and LPS. The expression pattern of 265 genes was significantly changed (up/down) in peritoneal macrophages extracted from wild type mice following treatment with IFN-γ and LPS, while no changes in the expression levels of these genes were observed in samples of the same cell-type from both IRF-1 and IRF-8 null mice. Among these putative target genes, numerous genes are involved in macrophage activity during inflammation. The expression profile of 10 of them was further examined by quantitative RT-PCR. In addition, the promoter regions of three of the identified genes were analyzed by reporter gene assay for the ability to respond to IRF-1 and IRF-8. Together, our results suggest that both IRF-1 and IRF-8 are involved in the transcriptional regulation of these genes. We therefore suggest a broader role for IRF-1 and IRF-8 in macrophages differentiation and maturation, being important inflammatory mediators.

Original languageEnglish
Pages (from-to)338-346
Number of pages9
JournalMolecular Immunology
Volume44
Issue number4
DOIs
StatePublished - Jan 2007
Externally publishedYes

Keywords

  • CXCL16
  • H28
  • ICSBP
  • IRF-1
  • IRF-8
  • Interferon regulatory factors (IRFs)
  • LIF
  • MAP4K4
  • MMP9
  • MYC
  • Macrophage activation
  • PCDH7
  • PML
  • SOCS7
  • Transcriptional regulation

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