| TGF-beta and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells. | |
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MedLine Citation:
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PMID: 15699136 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously demonstrated that agents known to signal infection or inflammation can rapidly and directly drive differentiation of human CD14+ monocytes into CD83+ dendritic cells (DCs) when introduced to cells under serum-free conditions. In this study, we evaluated the effects of TGF-beta and vitamin D3 (VitD3) on the proportion and function of monocytes that adopt DC characteristics. TGF-beta significantly decreased the proportion of cells that rapidly adopted stable DC characteristics in response to LPS, but had little or no effect on calcium ionophore-induced differentiation. In contrast, VitD3 showed no such pathway specificity and dramatically suppressed differentiation of monocytes into DCs in response to these agents. Both TGF-beta and VitD3 altered cytokine and chemokine production in LPS-treated monocytes, inhibited IL-12 and IL-10 secretion, and decreased the functional capacity of DCs. Despite the similar effects of TGF-beta and VitD3, there are significant differences in the signaling pathways used by these agents, as evidenced by their distinct effects on LPS- and calcium ionophore-induced DC differentiation, on LPS-induced secretion of IL-10, and on two members of the NF-kappaB family of transcription factors, RelB and cRel. These studies identify TGF-beta and VitD3 as potent regulatory factors that use distinct pathways to suppress both the differentiation of DCs as well as their capacity to secrete the Th1-polarizing cytokine IL-12. Because these agents are present in serum and negatively affect DC differentiation at physiological concentrations, our findings are likely to have significance regarding the in vivo role of TGF-beta and VitD3 in determining the type of immune responses. |
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Authors:
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Lyudmila A Lyakh; Michael Sanford; Sebel Chekol; Howard A Young; Anita B Roberts |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 174 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-02-08 Completed Date: 2005-03-29 Revised Date: 2009-11-19 |
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: 2061-70 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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immunology Antigen-Presenting Cells / immunology Antigens, CD Cell Differentiation / immunology Cells, Cultured Cholecalciferol / physiology* Culture Media, Serum-Free DNA-Binding Proteins / metabolism Dendritic Cells / immunology*, metabolism Down-Regulation / immunology Humans Immunoglobulins / biosynthesis* Immunologic Factors / physiology* Immunophenotyping Interleukin-12 / antagonists & inhibitors*, biosynthesis* Lipopolysaccharides / antagonists & inhibitors, pharmacology Lymphocyte Culture Test, Mixed Membrane Glycoproteins / biosynthesis* Monocytes / cytology, immunology, metabolism NF-kappa B / antagonists & inhibitors, metabolism Receptors, Cell Surface / biosynthesis Signal Transduction / immunology* Smad Proteins Toll-Like Receptors Trans-Activators / metabolism Transforming Growth Factor beta / physiology* p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/CD83 antigen; 0/Culture Media, Serum-Free; 0/DNA-Binding Proteins; 0/Immunoglobulins; 0/Immunologic Factors; 0/Lipopolysaccharides; 0/Membrane Glycoproteins; 0/NF-kappa B; 0/Receptors, Cell Surface; 0/Smad Proteins; 0/Toll-Like Receptors; 0/Trans-Activators; 0/Transforming Growth Factor beta; 187348-17-0/Interleukin-12; 67-97-0/Cholecalciferol; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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