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ERK activation following macrophage FcgammaR ligation leads to chromatin modifications at the IL-10 locus.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 Jul 01; Vol. 175 (1), pp. 469-77. - Publication Year :
- 2005
-
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 FcgammaR 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.
- Subjects :
- Animals
Antigen-Antibody Complex metabolism
Base Sequence
Binding Sites genetics
Chromatin genetics
Chromatin metabolism
Chromatin Assembly and Disassembly
DNA genetics
DNA metabolism
DNA-Binding Proteins metabolism
Enzyme Activation
Histones chemistry
Histones metabolism
In Vitro Techniques
Mice
Mice, Inbred BALB C
Phosphorylation
Promoter Regions, Genetic
STAT3 Transcription Factor
Serine chemistry
Sp1 Transcription Factor metabolism
Trans-Activators metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Interleukin-10 genetics
Macrophages enzymology
Macrophages immunology
Receptors, IgG metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 175
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15972681
- Full Text :
- https://doi.org/10.4049/jimmunol.175.1.469