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ERK Activation Following Macrophage FcγR Ligation Leads to Chromatin Modifications at the IL-10 Locus
Abstract
We have previously demonstrated that macrophages stimulated in the presence of immune complexes produce high levels of IL-10. We now examine the mechanism of IL-10 superinduction. We report that the enhanced production of IL-10 correlates with a rapid and enhanced activation of two MAPKs, ERK and p38. The inhibition of either ERK or p38 prevented IL-10 induction, indicating that both MAPKs were required for IL-10 synthesis. By chromatin immunoprecipitation assay, we demonstrate that activation of ERK leads to the phosphorylation of serine 10 on histone H3 at the il-10 gene, making the promoter more accessible to transcription factors generated in response to p38 activation. Inhibition of ERK activation prevented histone modifications, and decreased the binding of Sp1 and STAT3 to the IL-10 promoter. We conclude that the activation of ERK following FcγR ligation leads to a remodeling of the chromatin at the il-10 locus, making it more accessible to transcription factors. The rapid and transient regulation of transcription factor accessibility to the IL-10 promoter by MAPK activation represents a novel way that the production of this cytokine is regulated.
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“Published studies have shown that phosphorylation of histone H3 at the serine residue at position 10 (Ser10) is needed for transcriptional activation of the Il10 promoter24.”
From The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance (2009) · cites this paper as [24]
Citations
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Metadata
- Authors
- Lucas, M., Zhang, X., Prasanna, V., & Mosser, D. M.
- Affiliations
- University of Maryland, College Park (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-07-01
- Volume
- 175
- Issue
- 1
- Pages
- 469-477
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2142436167
- Cited by
- 197
- References
- 44
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 4 · 2015: 14 · 2014: 11 · 2013: 12 · 2012: 10
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI49383, R01AI049383)
- 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 › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- IL-10, macrophages, ERK activation, p38 MAPK, MAPK signaling, histone H3 serine 10 phosphorylation, chromatin remodeling, IL-10 promoter, Sp1, STAT3, immune complexes, cytokine gene regulation
- MeSH terms
- Animals, Antigen-Antibody Complex, Base Sequence, Binding Sites, Chromatin, DNA, DNA-Binding Proteins, Enzyme Activation, Histones, Macrophages, Mice, Inbred BALB C, Phosphorylation, Promoter Regions, Genetic, Serine, Trans-Activators, Sp1 Transcription Factor, Interleukin-10, Receptors, IgG, Chromatin Assembly and Disassembly, Extracellular Signal-Regulated MAP Kinases, STAT3 Transcription Factor, Mice, In Vitro Techniques
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