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Role of Stat3 in Lipopolysaccharide-Induced IL-10 Gene Expression
Abstract
IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive. IL-10 is regulated at the level of transcription, but the critical motifs and the relevant transcription factors controlling this gene have remained elusive to date. We now report that a sequence at −120 bp in the human IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced trans-activation. Overexpression of dominant negative Stat3 suppresses promoter activity, while wild-type Stat3 leads to an enhancement of this activity. Our results show that Stat3, by binding to a single motif in the IL-10 promoter, is controlling expression of the human IL-10 gene.
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“Pin1 enhances the activity of transcription factors, CREB and STAT3 in several cell types, which increase IL-10 production in macrophages [15], [16].”
From Prolyl Isomerase Pin1 Protects Mice from Endotoxin Shock (2011) · cites this paper as [16]
In the citing paper
“transcription factors known to interact with the Il10 promoter25,26.”
From The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance (2009) · cites this paper as [25]
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Metadata
- Authors
- Benkhart, E. M., Siedlar, M., Wedel, A., Werner, T., & Ziegler-Heitbrock, H. W. L.
- Affiliations
- Institut für Immunologie (DE)
- Instituto de Medicina Genómica (ES)
- Institute for Immunology, University of Munich , Munich ,
- Corresponding author
- Siedlar, Maciej
- Wedel, Angela
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08-01
- Volume
- 165
- Issue
- 3
- Pages
- 1612-1617
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1591670144
- Cited by
- 249
- References
- 24
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 9 · 2015: 6 · 2014: 9 · 2013: 8 · 2012: 19
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT3, IL-10, lipopolysaccharide, transcriptional regulation, promoter elements, dominant-negative STAT3, transcriptional activation, anti-inflammatory cytokines, transcription factors
- MeSH terms
- Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Genetic Vectors, Humans, Lipopolysaccharides, Promoter Regions, Genetic, Structure-Activity Relationship, Transcription, Genetic, Transfection, Signal Transduction, Transcriptional Activation, Trans-Activators, Mutagenesis, Site-Directed, Interleukin-10, Sequence Deletion, STAT3 Transcription Factor
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