title: Identification of IRF-8 and IRF-1 target genes in activated macrophages.
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-gamma 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-gamma 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.
authors.affiliation: Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Dror
authors.forename: Michal
authors.initials: M
authors.lastname: Alter-Koltunoff
authors.forename: Aviva
authors.initials: A
authors.lastname: Azriel
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Sharon
authors.initials: S
authors.lastname: Zeligson
authors.forename: Avigail
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Tamura
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Hauser
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Ben-Zion
authors.initials: BZ
authors.lastname: Levi
mesh_terms: D000818:Animals; D002460:Cell Line; D020869:Gene Expression Profiling; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000235:genetics*; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D000099185:Interferon Regulatory Factor-8
chemical_list: D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D000099185:Interferon Regulatory Factor-8