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• W1933610294 endingPage "453" @default.
• W1933610294 startingPage "445" @default.
• W1933610294 abstract "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." @default.
• W1933610294 created "2016-06-24" @default.
• W1933610294 creator A5005635984 @default.
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• W1933610294 date "2011-11-23" @default.
• W1933610294 modified "2023-10-12" @default.
• W1933610294 title "Adenosine Augments IL-10 Production by Microglial Cells through an A_2B Adenosine Receptor-Mediated Process" @default.
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• W1933610294 doi "https://doi.org/10.4049/jimmunol.1101224" @default.
• W1933610294 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3384725" @default.
• W1933610294 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22116830" @default.
• W1933610294 hasPublicationYear "2011" @default.
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