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Cutting Edge: A Transcriptional Repressor and Corepressor Induced by the STAT3-Regulated Anti-Inflammatory Signaling Pathway
Abstract
IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on proinflammatory mediator production. In this study we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3, and a helicase family corepressor, Strawberry notch homologue 2 (SBNO2), in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3 and a stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway regulated by IL-10 but not by STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 repressed NF-kappaB- but not IFN regulatory factor 7 (IRF7)-activated transcriptional reporters. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10.
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“STAT3 suppresses TLR signaling in mature phagocytes”
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Metadata
- Authors
- El Kasmi, K. C., Smith, A. M., Williams, L., Neale, G., Panopolous, A., Watowich, S. S., Häcker, H., Foxwell, B. M. J., & Murray, P. J.
- Affiliations
- Department of Infectious Diseases, St. Jude Children’s Research Hospital , Memphis, TN 38105
- St. Jude Children's Research Hospital (US)
- Imperial College London (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-01
- Volume
- 179
- Issue
- 11
- Pages
- 7215-7219
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2127303484
- Cited by
- 182
- References
- 30
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 13 · 2023: 15 · 2022: 9 · 2021: 15 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 10 · 2014: 6 · 2013: 11 · 2012: 14
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA009598, P 30CA 21765, P30CA021765, T32 CA09598-16)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-10, STAT3 signaling, transcriptional repressor, corepressors, anti-inflammatory signaling, macrophages, NF-κB, IRF7, interleukin-6
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Line, Gene Expression Regulation, Humans, Macrophages, Mice, Inbred C57BL, Repressor Proteins, RNA, Messenger, Time Factors, Transcription Factors, Signal Transduction, Interleukin-10, Mice, Knockout, RNA, Small Interfering, Proto-Oncogene Proteins c-ets, STAT3 Transcription Factor, Mice
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