Modulation of interferon consensus sequence binding protein mRNA in murine peritoneal macrophages. Induction by IFN-gamma and down-regulation by IFN-alpha, dexamethasone, and protein kinase inhibitors
Abstract
IFN play a central role in the activation of macrophages by inducing the expression of several proteins which, in turn, result in increased functional capabilities. Homologous interferon responsive sequences have been found in many IFN-inducible genes, and the gene for a protein that binds these sequences (interferon consensus sequence binding protein, ICSBP) has recently been cloned. In this study, the regulation of ICSBP mRNA induction by IFN-gamma was characterized in murine thioglycolate-elicited peritoneal macrophages. Northern blot analysis revealed two ICSBP mRNA species from these cells. Steady-state levels of both of these species were elevated by IFN-gamma at doses consistent with many IFN-gamma-induced macrophage functional responses. ICSBP mRNA levels increased within 1 h of IFN-gamma treatment, peaked between 4 and 6 h, and subsequently declined to approach baseline levels by approximately 24 h. IFN-alpha, at a concentration shown previously to modulate macrophage surface markers and functions, had no effect on ICSBP message levels alone, but antagonized the IFN-gamma-induction of ICSBP mRNA. IFN-gamma-induction of ICSBP mRNA is resistant to cycloheximide but sensitive to protein kinase inhibitors (H7, H8, HA-1004, staurosporine) at doses that suggest that protein kinase C is a likely target. ICSBP mRNA induction is also inhibited by dexamethasone, a synthetic glucocorticoid, well known as an anti-inflammatory drug capable of influencing gene expression in macrophages. The characterization of ICSBP mRNA regulation should help identify functions for this putative IFN trans-acting factor in macrophage activation.
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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 [9]
ICSBP is expressed in hematopoietic cells, including monocyte/macrophage lineage, B lymphocytes, and activated T lymphocytes, and is inducible by IFN-γ in these cells.
“ICSBP is expressed in the hematopoietic cells, including cells of the monocyte/macrophage lineage, B lymphocytes, and activated T lymphocytes, and is inducible by IFNg in these cells, suggesting its role in immune cells. (6,9-13)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [9]
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Zhang, M. (2008) · TigerPrints (Clemson University)
- Authors
- Politis, A. D., Sivo, J., Driggers, P. H., Ozato, K., & Vogel, S. N.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1992-02-01
- Volume
- 148
- Issue
- 3
- Pages
- 801-807
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1534412053
- Cited by
- 68
- References
- 0
- Citations by year
- 2025: 4 · 2024: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 1
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI-18797)
- 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
- interferon-gamma, interferon-alpha, peritoneal macrophages, macrophage activation, protein kinase C, protein kinase inhibitors, dexamethasone, glucocorticoids, cycloheximide, gene expression regulation, thioglycolate-elicited macrophages
- MeSH terms
- Interferon Regulatory Factor-8, Animals, Ascitic Fluid, Carrier Proteins, Dexamethasone, Dose-Response Relationship, Drug, Interferon-gamma, Macrophages, Recombinant Proteins, Repressor Proteins, RNA, Messenger, Gene Expression, Interferon-alpha, Protein Kinase Inhibitors, Interferon Regulatory Factors, Mice
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