ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Adenosine augments IL-10 production by microglial cells through an A2B adenosine receptor-mediated process.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 137 citations in OpenAlex.
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- The glioma microenvironment and its impact on antitumor immunity.Neuro-oncology advances · 2025Review
- Microglial purinergic signaling in Alzheimer's disease.Purinergic signalling · 2025Review
- Therapeutic potential of adenosine receptor modulators in cancer treatment.RSC advances · 2025Review
- APurinergic signalling · 2025Review
- MRS3997, a dual adenosine ANeuropharmacology · 2025Article
- Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy.Cancer biology & medicine · 2024Review
- Current Understanding of the Role of Adenosine Receptors in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Gene regulation in activated microglia by adenosine APurinergic signalling · 2024Article
- Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human.Cells · 2024Review
- Impaired olfactory performance and anxiety-like behavior in a rat model of multiple sclerosis are associated with enhanced adenosine signaling in the olfactory bulb via AFrontiers in cellular neuroscience · 2024Article
- Receptors on Microglia.Advances in neurobiology · 2024Review
- An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury.Advanced healthcare materials · 2023Article
- Adenosine signaling as target in cardiovascular pharmacology.Current opinion in pharmacology · 2023Review
- Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering ARespiratory research · 2023Article
- FUNDC1: a key mediator of adenosine A2BR activation-induced inhibition of cardiac mitophagy under ischemia/reperfusion conditions.Cardiovascular diagnosis and therapy · 2023Article
- May be adenosine an immuno-quorum-sensing signal?Purinergic signalling · 2022Article
- Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients.Frontiers in immunology · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.