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

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

doi:10.1016/j.molimm.2006.02.026

Cited by 75 publications

(68 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the last case, PU.1 might play an important role by increasing the transactivation of TNF-␣ promoter, through the cooperation of IRF-1 with IRF-8. Combined action of IRF-1 and IRF-8 (as well as PU.1) have been previously described in the induction of RANTES (57) and iNOS (19,58) by IFN-␥. Interestingly, TNF-␣ transcriptional activity induced by IRF-1 and IRF-8 is inhibited when the region between Ϫ173 and Ϫ120 bp was deleted.…”

Section: Discussionmentioning

confidence: 91%

IFN-γ-Induced TNF-α Expression Is Regulated by Interferon Regulatory Factors 1 and 8 in Mouse Macrophages

Sol

Punzón

Fresno

2008

The Journal of Immunology

129

View full text Add to dashboard Cite

We have previously described that IFN-γ induces cyclooxygenase 2 and inducible NO synthase expression by a mechanism that involved endogenously produced TNF-α. In this study, we report that TNF-α production is induced by IFN-γ treatment in the murine macrophage cell line RAW 264.7. TNF-α mRNA levels are increased in cells treated with IFN-γ in a time-dependent manner and IFN-γ also increased human TNF-α promoter-dependent transcription. Two regions in the TNF-α promoter seem to be responsible for the IFN-γ response: a distal region between −1311 and −615 bp of the human TNF-α promoter, and a proximal region located between −95 and −36 bp upstream of the transcriptional start. In contrast, IFN-γ stimulation induces the expression of the transcription factors IRF-1 and IRF-8. Overexpression of these transcription factors produces an increase in the transcriptional activity of the human TNF-α promoter. There is a correlation between the regions of the TNF-α promoter responsible of the transcriptional activation elicited by IRF-1 and IRF-8 and those required for IFN-γ response. In addition, IRF-1 and IRF-8 are recruited to the TNF-α promoter in IFN-γ-treated RAW 264.7 cells, as demonstrated by chromatin immunoprecipitation assays. Moreover, overexpression of IRF-1 and IRF-8 induces TNF-α production in unstimulated RAW 264.7 macrophages, comparable to the production of TNF-α elicited by IFN-γ stimulation, and silencing of IRF-1 and/or IRF-8 with specific small interfering RNAs, decreases IFN-γ-elicited TNF-α production. In summary, IFN-γ treatment induces TNF-α expression at transcriptional level requiring the coordinate action of IRF-1 and IRF-8.

show abstract

Section: Discussionmentioning

confidence: 91%

IFN-γ-Induced TNF-α Expression Is Regulated by Interferon Regulatory Factors 1 and 8 in Mouse Macrophages

Sol

Punzón

Fresno

2008

The Journal of Immunology

129

View full text Add to dashboard Cite

show abstract

“…For this purpose, we compared the expression profile of genes in peritoneal macrophages from WT and from IRF-8 Ϫ/Ϫ mice, before and following 4 h of stimulation with IFN-␥ and LPS. This analysis led to the identification of PML as a putative gene regulated by IRF-8 in activated macrophages (18). To further validate these results, Northern blot analyses were performed using nonstimulated as well as stimulated peritoneal macrophages and the macrophage cell lines RAW264.7 (expressing IRF-8) and CL-2 (originating from IRF-8 KO mice (28)).…”

Section: Irf-8 Is Essential For the Induced Expression Of Pml In Macrmentioning

confidence: 99%

“…Organs-To identify genes that are regulated by IRF-8 and IRF-1 in macrophages, DNA microarray analysis was employed (18). For this purpose, we compared the expression profile of genes in peritoneal macrophages from WT and from IRF-8 Ϫ/Ϫ mice, before and following 4 h of stimulation with IFN-␥ and LPS.…”

Section: Irf-8 Is Essential For the Induced Expression Of Pml In Macrmentioning

confidence: 99%

“…To characterize the IRF-8 regulatory network in activated macrophages, a differential expression profile of peritoneal macrophages extracted from wild type (WT) mice versus IRF-8 Ϫ/Ϫ mice, before and following 4 h of stimulation with IFN-␥ and LPS, was studied using DNA microarray assay (18). Among the many putative IRF-8-target genes, the promyelocytic leukemia (PML) gene was identified.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interferon Regulatory Factor-8 Is Indispensable for the Expression of Promyelocytic Leukemia and the Formation of Nuclear Bodies in Myeloid Cells

Dror

Rave-Harel

Burchert

et al. 2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Interferon (IFN) regulatory factor-8 (IRF-8), previously known as ICSBP, is a myeloid cell essential transcription factor. Mice with null mutation in IRF-8 are defective in the ability of myeloid progenitor cells to mature toward macrophage lineage. Accordingly, these mice develop chronic myelogenous leukemia (CML). We demonstrate here that IRF-8 is an obligatory regulator of the promyelocytic leukemia (PML) gene in activated macrophages, leading to the expression of the PML-I isoform. This regulation is most effective together with two other transcription factors, IRF-1 and PU.1. PML is a tumor suppressor gene that serves as a scaffold protein for nuclear bodies. IRF-8 is not only essential for the IFN-␥-induced expression of PML in activated macrophages but also for the formation of nuclear bodies. Reduced IRF-8 transcript levels were reported in CML patients, and a recovery to normal levels was observed in patients in remission following treatment with IFN-␣. We demonstrate a significant correlation between the levels of IRF-8 and PML in these CML patients. Together, our results indicate that some of the myeloleukemia suppressor activities of IRF-8 are mediated through the regulation of PML. When IRF-8 levels are compromised, the reduced PML expression may lead to genome instability and eventually to the leukemic phenotype.

show abstract

“…Indeed, Irf1 or Irf8 mutant macrophages are susceptible to infection with intracellular pathogens (Fehr et al, 1997;Cooper et al, 2000;Marquis et al, 2009b). Transactivation experiments with target genes have shown that IRF8 and IRF1 functionally interact for IFN-γ-induced activation of certain genes involved in macrophage antimicrobial defenses and in production of inflammatory cytokines that activate early immune responses (Dror et al, 2007). At the molecular level, IRF8 is known to be corecruited to ternary complexes with other transcription factors (TFs) such as (a) IRF1 and IRF2 that bind to IFN-stimulated response elements (ISREs; GAAAnnGAAA; Bovolenta et al, 1994), (b) AP-1 family members that bind to AP1-IRF composite elements (TGAnnnGAAA or GAA ATGA; Glasmacher et al, 2012;Li et al, 2012), or (c) Ets family members such as PU.1 that are required for the development of lymphoid and myeloid lineages (Scott et al, 1994;McKercher et al, 1996) and that bind to Ets-IRF composite elements (EICEs; GGAAnnGAAA).…”

mentioning

confidence: 99%

The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation

Langlais¹,

Barreiro²,

Gros³

2016

J Cell Biol

View full text Add to dashboard Cite

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

Cited by 75 publications

References 47 publications

IFN-γ-Induced TNF-α Expression Is Regulated by Interferon Regulatory Factors 1 and 8 in Mouse Macrophages

IFN-γ-Induced TNF-α Expression Is Regulated by Interferon Regulatory Factors 1 and 8 in Mouse Macrophages

Interferon Regulatory Factor-8 Is Indispensable for the Expression of Promyelocytic Leukemia and the Formation of Nuclear Bodies in Myeloid Cells

The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation

Contact Info

Product

Resources

About