| Differential modulation of TLR3- and TLR4-mediated dendritic cell maturation and function by progesterone. | |
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MedLine Citation:
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PMID: 20844199 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of progesterone in modulating dendritic cell (DC) function following stimulation of different TLRs is relatively unknown. We compared the ability of progesterone to modulate murine bone marrow-derived DC cytokine production (IL-6 and IL-12) and costimulatory molecule expression (CD40, CD80, and CD86) induced by either TLR3 or TLR4 ligation and determined whether activity was via the progesterone receptor (PR) or glucocorticoid receptor (GR) by comparative studies with the PR-specific agonist norgestrel and the GR agonist dexamethasone. Progesterone was found to downregulate, albeit with different sensitivities, both TLR3- and TLR4-induced IL-6 production entirely via the GR, but IL-12p40 production via either the GR or PR. Of particular significance was that progesterone was able to significantly inhibit TLR3- but not TLR4-induced CD40 expression in bone marrow-derived DCs. Stimulation of the PR (with progesterone and norgestrel) by pretreatment of DCs was found to sustain IFN regulatory factor-3 phosphorylation following TLR3 ligation, but not TLR4 ligation. Overall, these studies demonstrate that progesterone can differentially regulate the signaling pathways employed by TLR3 and TLR4 agonists to affect costimulatory molecule expression and cytokine production. |
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Authors:
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Leigh A Jones; Shrook Kreem; Muhannad Shweash; Andrew Paul; James Alexander; Craig W Roberts |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-15 |
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 Oct |
Date Detail:
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Created Date: 2010-10-06 Completed Date: 2010-11-04 Revised Date: - |
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: 4525-34 Citation Subset: AIM; IM |
Affiliation:
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Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Differentiation / drug effects, immunology Cytokines / biosynthesis Dendritic Cells / cytology, immunology, metabolism* Enzyme-Linked Immunosorbent Assay Male Mice Mice, Inbred BALB C Progesterone / metabolism*, pharmacology Receptors, Glucocorticoid / immunology, metabolism Receptors, Progesterone / immunology, metabolism Signal Transduction / drug effects, immunology* Toll-Like Receptor 3 / drug effects, immunology, metabolism* Toll-Like Receptor 4 / drug effects, immunology, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Receptors, Glucocorticoid; 0/Receptors, Progesterone; 0/TLR3 protein, mouse; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 3; 0/Toll-Like Receptor 4; 57-83-0/Progesterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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