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Cited by 187interferon and immune responsesCytokine Signaling Pathways and InteractionsImmune Response and Inflammation

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

Wang, I-Ming, Contursi, Cristina, Masumi, Atsuko, Ma, Xiaojing, Trinchieri, Giorgio, Ozato, Keiko·2000·The Journal of Immunology
DOI 10.4049/jimmunol.165.1.271
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Abstract

IL-12 is a cytokine that links innate and adaptive immunity. Its subunit p40 is induced in macrophages following IFN-γ/LPS stimulation. Here we studied the role for IFN consensus sequence binding protein (ICSBP), an IFN-γ/LPS-inducible transcription factor of the IFN regulatory factor (IRF) family in IL-12 p40 transcription. Macrophage-like cells established from ICSBP−/− mice did not induce IL-12 p40 transcripts, nor stimulated IL-12 p40 promoter activity after IFN-γ/LPS stimulation, although induction of other inducible genes was normal in these cells. Transfection of ICSBP led to a marked induction of both human and mouse IL-12 p40 promoter activities in ICSBP+/+ and ICSBP−/− cells, even in the absence of IFN-γ/LPS stimulation. Whereas IRF-1 alone was without effect, synergistic enhancement of promoter activity was observed following cotransfection of ICSBP and IRF-1. Deletion analysis of the human promoter indicated that the Ets site, known to be important for activation by IFN-γ/LPS, also plays a role in the ICSBP activation of IL-12 p40. A DNA affinity binding assay revealed that endogenous ICSBP is recruited to the Ets site through protein-protein interaction. Last, transfection of ISCBP alone led to induction of the endogenous IL-12 p40 mRNA in the absence of IFN-γ and LPS. Taken together, our results show that ICSBP induced by IFN-γ/LPS, acts as a principal activator of IL-12p40 transcription in macrophages.

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Crossref · 10.4049/jimmunol.165.1.271

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  • ICSBP/IRF-8 is an IFN-γ-inducible transcription factor of the IRF family that regulates transcription through multiple target DNA elements, including ISRE, EICE, and GAS.

    “Interferon (IFN) consensus sequence binding protein (ICSBP)/IFN regulatory factor (IRF)-8 is an IFN g -inducible transcription factor of the IRF family and regulates transcription through multiple target DNA elements, such as IFN-stimulated response element (ISRE), Ets/IRF composite element, and IFNg activation site (GAS).”

    From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [15]

  • ICSBP can act on a wide range of target elements beyond the IRS, such as the Ets site in the IL-12 p40 promoter and the IFN-γ activation site (GAS).

    “Recent studies indicate that ICSBP can act on a wide range of target elements even beyond the IRS, such as the Ets site in IL-12 p40 promoter and the IFNg activation site (GAS). (15,34)”

    From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [15]

  • LPS also induces ICSBP, albeit to a lesser degree, and synergizes with IFN-γ in macrophages.

    “Lipopolysaccharide (LPS) also induces ICSBP, albeit to a lesser degree, and synergizes with IFNg in macrophages. (13-15)”

    From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [15]

  • ICSBP alone is able to activate mouse and human IL-12 p40 promoters, acting through the Ets site, and exogenous IRF-1 synergizes with ICSBP.

    “It was shown that ICSBP alone is able to activate mouse and human IL-12 p40 promoters.”

    From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [15]

  • ICSBP interacts with IRF-1 and IRF-2 and antagonizes IRF-1 activation of promoters through the standard ISRE.

    “ICSBP also interacts with IRF-1 and IRF-2 and antagonizes IRF-1 activation of promoters through the standard ISRE.”

    From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [15]

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Authors
Wang, I.-M., Contursi, C., Masumi, A., Ma, X., Trinchieri, G., & Ozato, K.
Affiliations
  • National Institutes of Health (US)
  • The Wistar Institute (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2000-07-01
Volume
165
Issue
1
Pages
271-279
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.165.1.271
OpenAlex
W1592326302
Cited by
187
References
55
Citations by year
2026: 5 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 5 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 5
FWCI
5.07
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
IRF8, IL-12p40, macrophages, interferon-gamma, LPS, IRF1, protein-protein interaction, transcriptional activation, innate and adaptive immunity
MeSH terms
Interferon Regulatory Factor-8, Animals, Cell Line, DNA-Binding Proteins, Drug Synergism, Gene Expression Regulation, Humans, Interferon-gamma, Lipopolysaccharides, Macrophages, Phosphoproteins, Promoter Regions, Genetic, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Transfection, Transcriptional Activation, Consensus Sequence, Mice, Knockout, Interleukin-12, Macromolecular Substances, Proto-Oncogene Proteins c-ets, Interferon Regulatory Factors, Interferon Regulatory Factor-2, Interferon Regulatory Factor-1, Mice

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