2.50
Hdl Handle:
http://hdl.handle.net/10033/19773
Title:
Identification of IRF-8 and IRF-1 target genes in activated macrophages.
Authors:
Dror, Natalie; Alter-Koltunoff, Michal; Azriel, Aviva; Amariglio, Ninette; Jacob-Hirsch, Jasmine; Zeligson, Sharon; Morgenstern, Avigail; Tamura, Tomohiko; Hauser, Hansjörg; Rechavi, Gideon; Ozato, Keiko; Levi, Ben-Zion
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.
Affiliation:
Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
Citation:
Identification of IRF-8 and IRF-1 target genes in activated macrophages. 2007, 44 (4):338-46 Mol. Immunol.
Journal:
Molecular immunology
Issue Date:
Jan-2007
URI:
http://hdl.handle.net/10033/19773
DOI:
10.1016/j.molimm.2006.02.026
PubMed ID:
16597464
Type:
Article
Language:
en
ISSN:
0161-5890
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValue Language
dc.contributor.authorDror, Natalie-
dc.contributor.authorAlter-Koltunoff, Michal-
dc.contributor.authorAzriel, Aviva-
dc.contributor.authorAmariglio, Ninette-
dc.contributor.authorJacob-Hirsch, Jasmine-
dc.contributor.authorZeligson, Sharon-
dc.contributor.authorMorgenstern, Avigail-
dc.contributor.authorTamura, Tomohiko-
dc.contributor.authorHauser, Hansjörg-
dc.contributor.authorRechavi, Gideon-
dc.contributor.authorOzato, Keiko-
dc.contributor.authorLevi, Ben-Zion-
dc.date.accessioned2008-03-05T10:06:02Z-
dc.date.available2008-03-05T10:06:02Z-
dc.date.issued2007-01-
dc.identifier.citationIdentification of IRF-8 and IRF-1 target genes in activated macrophages. 2007, 44 (4):338-46 Mol. Immunol.en
dc.identifier.issn0161-5890-
dc.identifier.pmid16597464-
dc.identifier.doi10.1016/j.molimm.2006.02.026-
dc.identifier.urihttp://hdl.handle.net/10033/19773-
dc.description.abstractInterferon 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.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCell Lineen
dc.subject.meshGene Expression Profilingen
dc.subject.meshInterferon Regulatory Factor-1en
dc.subject.meshInterferon Regulatory Factorsen
dc.subject.meshInterferon Type IIen
dc.subject.meshLipopolysaccharidesen
dc.subject.meshMacrophage Activationen
dc.subject.meshMacrophages, Peritonealen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshPromoter Regions (Genetics)en
dc.subject.meshTrans-Activation (Genetics)en
dc.titleIdentification of IRF-8 and IRF-1 target genes in activated macrophages.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.en
dc.identifier.journalMolecular immunologyen
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