Cited by 250Genomics and Chromatin DynamicsCytokine Signaling Pathways and InteractionsT-cell and B-cell Immunology

IL-10 Gene Expression Is Controlled by the Transcription Factors Sp1 and Sp3

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Tone, Masahide, Powell, Mark J, Tone, Yukiko, Thompson, Sara A J, Waldmann, Herman·2000·The Journal of Immunology

Abstract

IL-10 is an 18-kDa cytokine with a key role in homeostatic control of inflammatory and immune responses. We have investigated how transcription of the IL-10 gene is regulated, so as to be able to understand the circumstances of IL-10 expression in both health and disease. In the mouse, IL-10 gene expression is regulated by a TATA-type promoter with a critical cis-acting element containing GGA repeats located at −89 to −77. Its complementary sequence is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and CD58. All these elements comprise a common CCTCCT sequence with less conserved C + T-rich sequences. Eliminating this CCTCCT sequence results in a marked reduction in promoter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Sp1 consensus sequence (GC box), Sp1 and Sp3 transcription factors could be shown to bind to this motif. The requirement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Drosophila SL2 cells, which lack endogenous Sp factors. These results suggest that the transcription of IL-10 is positively regulated by both Sp1 and Sp3.

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References 42 · Cited by 250

Authors
Tone, M., Powell, M. J., Tone, Y., Thompson, S. A. J., & Waldmann, H.
Affiliations
University of Oxford (GB)
Venue
The Journal of Immunology
Published
2000-07-01
Volume
165
Issue
1
Pages
286-291
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1817548159
Cited by
250
References
42
Citations by year
2025: 4 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 9 · 2014: 14 · 2013: 11 · 2012: 9
FWCI
4.10
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
IL-10, transcriptional regulation, Sp1, Sp3, promoter cis-acting elements, TATA box, Sp1 binding site, cytokine expression
MeSH terms
Animals, Base Sequence, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors, Sp1 Transcription Factor, Interleukin-10, 5' Untranslated Regions, Mice, Sp3 Transcription Factor

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