TY - JOUR
T1 - Identification of IRF-8 and IRF-1 target genes in activated macrophages
AU - Dror, Natalie
AU - Alter-Koltunoff, Michal
AU - Azriel, Aviva
AU - Amariglio, Ninette
AU - Jacob-Hirsch, Jasmine
AU - Zeligson, Sharon
AU - Morgenstern, Avigail
AU - Tamura, Tomohiko
AU - Hauser, Hansjörg
AU - Rechavi, Gideon
AU - Ozato, Keiko
AU - Levi, Ben Zion
N1 - Funding Information:
We are grateful to the Arison family donation to the center of DNA Chips, Pediatric Oncology, Chaim Sheba Medical Center and to Prof. Rubinstein from the Weizmann Institute for the generous gift of IRF-1 −/− mice. We thank Dr. Naama Rave-Harel from our laboratory for critical reading of the manuscript, and Dr. Shifra Ben-Dor from the Weizmann Institute for valuable help in data analysis. GR holds the Djerassi Chair in Oncology at the Sackler School of Medicine, and B.Z. Levi is an incumbent of the Lily and Silvian Marcus Chair in Life Sciences at the Technion. This research was partially funded by The Israel Science Foundation (Grant Number: 536/01), by the Center for the Study of Emerging Diseases (CSED), and the fund for the promotion of research at the Technion.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - CXCL16
KW - H28
KW - ICSBP
KW - IRF-1
KW - IRF-8
KW - Interferon regulatory factors (IRFs)
KW - LIF
KW - MAP4K4
KW - MMP9
KW - MYC
KW - Macrophage activation
KW - PCDH7
KW - PML
KW - SOCS7
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=33748131877&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2006.02.026
DO - 10.1016/j.molimm.2006.02.026
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:33748131877
SN - 0161-5890
VL - 44
SP - 338
EP - 346
JO - Molecular Immunology
JF - Molecular Immunology
IS - 4
ER -