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G. I. Liou, J. A. Auchampach, C. J. Hillard, G. Zhu, B. Yousufzai, S. Mian, S. Khan, Y. Khalifa; Mediation of Cannabidiol Immunosuppression by Adenosine Receptor A2a in Retinal Microglia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4893.
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Cannabidiol (CBD), a non-psychotropic, non-toxic compound has been shown to block diabetes-induced retinal damage, but the protective mechanism of this anti-inflammatory cannabinoid is not completely understood. This study is to determine the role of adenosine signaling in retinal inflammation and its modulation by CBD.
Expression and function of adenosine receptors in the rat retinal microglia was quantified via in vitro inflammatory models. The isotype of adenosine receptor that was upregulated under stressful inflammatory conditions was assessed by quantitative real-time RT-PCR. Cells were treated with or without lipopolysaccharide (LPS) in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. TNF-α release and adenosine uptake were assayed.
Our results showed that whereas the expression of the adenosine receptors A1AR, A2BAR, and A3AR was not detectable above background levels, A2AAR was the most highly expressed in the microglial cells. Upon LPS treatment of the cells, A2AAR was the most efficient in mediating TNF-α inhibition. CBD dose-dependently inhibited adenosine uptake and, as a result, synergistically enhanced adenosine’s TNF-α suppression upon LPS treatment.
These results suggest that activated A2AAR downregulates TNF-α release, and that CBD anti-inflammatory effects are linked to adenosine uptake inhibition.
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