| First Author | Koscsó B | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 1 | Pages | 445-53 |
| PubMed ID | 22116830 | Mgi Jnum | J:180826 |
| Mgi Id | MGI:5307951 | Doi | 10.4049/jimmunol.1101224 |
| Citation | Koscso B, et al. (2012) Adenosine augments IL-10 production by microglial cells through an A2B adenosine receptor-mediated process. J Immunol 188(1):445-53 |
| abstractText | Microglia are activated by pathogen-associated molecular patterns and produce proinflammatory cytokines, such as TNF-alpha, 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-alpha 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. |
