Cited by 197Cytokine Signaling Pathways and InteractionsGenomics and Chromatin DynamicsMonoclonal and Polyclonal Antibodies Research

ERK Activation Following Macrophage FcγR Ligation Leads to Chromatin Modifications at the IL-10 Locus

Lucas, Mark, Zhang, Xia, Prasanna, Vikram, Mosser, David M·2005·The Journal of Immunology

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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Crossref · 10.4049/jimmunol.175.1.469

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Authors
Lucas, M., Zhang, X., Prasanna, V., & Mosser, D. M.
Affiliations
University of Maryland, College Park (US)
Venue
The Journal of Immunology
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
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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