ArticleMolecular and cellular biology2004
Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Regulatory T cells: From Foxp3 to tolerance-inducing therapies.The Journal of investigative dermatology · 2026Review
- Regulatory roles of MKP7/DUSP16 in cancer.Medical oncology (Northwood, London, England) · 2025Review
- Biomarkers of Probiotic Therapy in Ulcerative Colitis: A Systematic Review of Mechanisms Underlying Remission.Cureus · 2025Review
- Deficiency of IL-20 receptor subunit A decreases enterovirus A71 lethality in mice by increasing M1 macrophage polarization and cytokine production.Frontiers in immunology · 2025Article
- Review
- Toll-Like Receptor 2-Tpl2-Dependent ERK Signaling Drives Inverse Interleukin 12 Regulation in Dendritic Cells and Macrophages.Infection and immunity · 2020Article
- Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5.EBioMedicine · 2016Article
- Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection.PLoS pathogens · 2016Article
- TNF Counterbalances the Emergence of M2 Tumor Macrophages.Cell reports · 2015Article
- Control of IL-17 receptor signaling and tissue inflammation by the p38α-MKP-1 signaling axis in a mouse model of multiple sclerosis.Science signaling · 2015Article
- Adenosine 5'-monophosphate-activated protein kinase regulates IL-10-mediated anti-inflammatory signaling pathways in macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Alterations of dendritic cells in sepsis: featured role in immunoparalysis.BioMed research international · 2015Review
- Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner.The Journal of biological chemistry · 2014Article
- Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex.The EMBO journal · 2014Article
- Early induction of interleukin-10 limits antigen-specific CD4⁺ T cell expansion, function, and secondary recall responses during persistent phagosomal infection.Infection and immunity · 2014Article
- Gene trap mice reveal an essential function of dual specificity phosphatase Dusp16/MKP-7 in perinatal survival and regulation of Toll-like receptor (TLR)-induced cytokine production.The Journal of biological chemistry · 2014Article
- Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways.Nature immunology · 2012Review
- IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.PLoS pathogens · 2012Article
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Authors and funding
3 authors.
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Abstract
Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that suppresses the induction of proinflammatory cytokine genes, including the IL-12 p40 gene. Despite considerable effort examining the effect of IL-10 on specific transcription factors and signaling molecules, the mechanism by which IL-10 inhibits gene transcription has remained elusive. To provide a different perspective to this problem, we examined the effect of IL-10 on molecular events occurring at the endogenous IL-12 p40 locus in lipopolysaccharide-stimulated peritoneal macrophages. IL-10 abolished recruitment of RNA polymerase II to the p40 promoter. However, it only modestly reduced binding of C/EBPbeta, as monitored by genomic footprinting and chromatin immunoprecipitation. It also had little effect on NF-kappaB complexes that are critical for p40 induction. A substantial reduction in nucleosome remodeling at the p40 promoter was observed, but the magnitude of this reduction appeared insufficient to account for the strong inhibition of transcription. Finally, a lipopolysaccharide-inducible DNase I hypersensitive site identified 10 kb upstream of the start site was unaffected by IL-10. Thus, despite a dramatic reduction in p40 transcription, several events required for activation of the endogenous p40 gene occurred relatively normally. These findings suggest that IL-10 blocks one or more events that occur after p40 locus decondensation and nucleosome remodeling and after, or in parallel with, the binding of a subset of p40 transcriptional activators.
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