| Lipopolysaccharide-mediated IL-10 transcriptional regulation requires sequential induction of type I IFNs and IL-27 in macrophages. | |
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MedLine Citation:
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PMID: 21041726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-10 is a potent anti-inflammatory molecule that regulates excessive production of inflammatory cytokines during an infection or tissue damage. Dysregulation of IL-10 is associated with a number of autoimmune diseases, and so, understanding the mechanisms by which IL-10 gene expression is regulated remains an important area of study. Macrophages represent a major source of IL-10, which is generated in response to TLR signaling as a feedback mechanism to curtail inflammatory response. In this study, we identify a signaling pathway in murine bone marrow-derived macrophages in which activation of TLR4 by LPS induces the expression of IL-10 through the sequential induction of type I IFNs followed by induction and signaling through IL-27. We demonstrate that IL-27 signaling is required for robust IL-10 induction by LPS and type I IFNs. IL-27 leads directly to transcription of IL-10 through the activation of two required transcription factors, STAT1 and STAT3, which are recruited to the IL-10 promoter. Finally, through systematic functional promoter-reporter analysis, we identify three cis elements within the proximal IL-10 promoter that play an important role in regulating transcription of IL-10 in response to IL-27. |
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Authors:
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Shankar Subramanian Iyer; Amir Ali Ghaffari; Genhong Cheng |
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Publication Detail:
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Type: Journal Article Date: 2010-11-01 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2011-01-10 Revised Date: 2011-03-17 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6599-607 Citation Subset: AIM; IM |
Affiliation:
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Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autocrine Communication / genetics, immunology Bone Marrow Cells / immunology, metabolism Cell Line Interferon Type I / biosynthesis*, genetics Interleukin-10 / genetics*, metabolism Interleukins / biosynthesis*, genetics, physiology Lipopolysaccharides / pharmacology* Macrophages / immunology*, metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Paracrine Communication / genetics, immunology Promoter Regions, Genetic / immunology* Signal Transduction / genetics, immunology Transcription, Genetic / immunology* Transcriptional Activation / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI056154-07/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Il27 protein, mouse; 0/Interferon Type I; 0/Interleukins; 0/Lipopolysaccharides; 130068-27-8/Interleukin-10 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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