| Adenosine augments IL-10 production by microglial cells through an A2B adenosine receptor-mediated process. | |
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MedLine Citation:
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PMID: 22116830 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Microglia are activated by pathogen-associated molecular patterns and produce proinflammatory cytokines, such as TNF-α, IL-6, and IL-12, and the anti-inflammatory cytokine IL-10. Adenosine is an endogenous purine nucleoside and a ligand of four G protein-coupled adenosine receptors (ARs), which are the A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR. ARs have been shown to suppress TNF-α production by microglia, but their role in regulating IL-10 production has not been studied. In this study, we demonstrate that adenosine augments IL-10 production by activated murine microglia while suppressing the production of proinflammatory cytokines. Because the order of potency of selective AR agonists in inducing IL-10 production was NECA > IB-MECA > CCPA ≥ CGS21680, and the A(2B)AR antagonist MRS1754 prevented the effect of NECA, we conclude that the stimulatory effect of adenosine on IL-10 production is mediated by the A(2B)AR. Mechanistically, adenosine augmented IL-10 mRNA accumulation by a transcriptional process. Using mutant IL-10 promoter constructs we showed that a CREB-binding region in the promoter mediated the augmenting effect of adenosine on IL-10 transcription. Chromatin immunoprecipitation analysis demonstrated that adenosine induced CREB phosphorylation at the IL-10 promoter. Silencing CREB using lentivirally delivered short hairpin RNA blocked the enhancing effect of adenosine on IL-10 production, confirming a role for CREB in mediating the stimulatory effect of adenosine on IL-10 production. In addition, adenosine augmented IL-10 production by stimulating p38 MAPK. Collectively, our results establish that A(2B)ARs augment IL-10 production by activated murine microglia. |
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Authors:
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Balázs Koscsó; Balázs Csóka; Zsolt Selmeczy; Leonóra Himer; Pál Pacher; László Virág; György Haskó |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-11-23 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 188 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-21 Completed Date: 2012-02-16 Revised Date: 2013-04-01 |
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: 445-53 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetamides
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pharmacology Adenosine / immunology*, pharmacology Adenosine A2 Receptor Agonists / immunology, pharmacology Adenosine A2 Receptor Antagonists / pharmacology Analgesics / immunology, pharmacology Animals CREB-Binding Protein / immunology, metabolism Cell Line Interleukin-10 / biosynthesis, immunology* MAP Kinase Signaling System / drug effects, immunology* Mice Microglia / cytology, immunology*, metabolism Nerve Tissue Proteins / agonists, antagonists & inhibitors, immunology*, metabolism Phosphorylation / drug effects, immunology Promoter Regions, Genetic / immunology Purines / pharmacology RNA, Messenger / biosynthesis, immunology Receptor, Adenosine A2B / immunology*, metabolism Transcription, Genetic / drug effects, immunology p38 Mitogen-Activated Protein Kinases / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM066189/GM/NIGMS NIH HHS; R01 GM066189-08/GM/NIGMS NIH HHS; R01GM66189/GM/NIGMS NIH HHS; R56 GM066189/GM/NIGMS NIH HHS; Z99 AA999999/AA/NIAAA NIH HHS; ZIA AA000375-06/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetamides; 0/Adenosine A2 Receptor Agonists; 0/Adenosine A2 Receptor Antagonists; 0/Analgesics; 0/Crebbp protein, mouse; 0/IL10 protein, mouse; 0/N-(4-cyanophenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy)acetamide; 0/Nerve Tissue Proteins; 0/Purines; 0/RNA, Messenger; 0/Receptor, Adenosine A2B; 130068-27-8/Interleukin-10; 58-61-7/Adenosine; EC 2.3.1.48/CREB-Binding Protein; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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