ArticleJournal of immunology (Baltimore, Md. : 1950)2005
Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism.
Article in Journal of immunology (Baltimore, Md. : 1950), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 285 citations in OpenAlex.
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- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine.Cell reports · 2025Article
- Protective effect of adenosine triphosphate against cisplatin-induced necrotic and degenerative oral mucositis in rats.Journal of applied oral science : revista FOB · 2025Article
- Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy.Cancer biology & medicine · 2024Review
- An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.Cell reports · 2024Article
- Glioprotective Effects of Sulforaphane in Hypothalamus: Focus on Aging Brain.Neurochemical research · 2024Article
- CD73/adenosine dynamics in treatment-induced pneumonitis: balancing efficacy with risks of adverse events in combined radio-immunotherapies.Frontiers in cell and developmental biology · 2024Review
- A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.International journal of biological sciences · 2024Review
- Adenosine-mediated immune responses in inflammatory bowel disease.Frontiers in cell and developmental biology · 2024Review
- Mesenchymal Stem Cell-Macrophage Crosstalk Provides Specific Exosomal Cargo to Direct Immune Response Licensing of Macrophages during Inflammatory Responses.Stem cell reviews and reports · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Adenosine receptor ligands have anti-inflammatory effects and modulate immune responses by up-regulating IL-10 production by immunostimulated macrophages. The adenosine receptor family comprises G protein-coupled heptahelical transmembrane receptors classified into four types: A1, A2A, A2B, and A3. Our understanding of the signaling mechanisms leading to enhanced IL-10 production following adenosine receptor occupancy on macrophages is limited. In this study, we demonstrate that adenosine receptor occupancy increases IL-10 production by LPS-stimulated macrophages without affecting IL-10 promoter activity and IL-10 mRNA levels, indicating a posttranscriptional mechanism. Transfection experiments with reporter constructs containing sequences corresponding to the AU-rich 3'-untranslated region (UTR) of IL-10 mRNA confirmed that adenosine receptor activation acts by relieving the translational repressive effect of the IL-10 3'-UTR. By contrast, adenosine receptor activation failed to liberate the translational arrest conferred by the 3'-UTR of TNF-alpha mRNA. The IL-10 3'-UTR formed specific complexes with proteins present in cytoplasmic extracts of RAW 264.7 cells. Adenosine enhanced binding of proteins to a region of the IL-10 3'-UTR containing the GUAUUUAUU nonamer. The stimulatory effect of adenosine on IL-10 production was mediated through the A(2B) receptor, because the order of potency of selective agonists was 5'-N-ethylcarboxamidoadenosine (NECA) > N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) > 2-chloro-N6-cyclopentyladenosine (CCPA) = 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine (CGS-21680). Also, the selective A2B antagonist, alloxazine, prevented the effect of adenosine. Collectively, these studies identify a novel pathway in which activation of a G protein-coupled receptor augments translation of an anti-inflammatory gene.
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Registered trials
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.