炎症歯周組織における内因性アデノシンの抗炎症作用の解析 : 歯肉線維芽細胞におけるアデノシンレセプター活性化の制御機構

概要

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Adenosine (Ado) has various biological effects on human gingival fibroblasts (HGF) and epithelial cells, that are closely associated with inflammation. However, little is known regarding mechanisms by which Ado action is regulated. In this study we examined the involvement of CD73 and ecto-adenosine deaminase (ADA) in metabolizing Ado and thus regulating AdoR activation in HGF. Adenosine production was observed following the addition of 5-AMP, a substrate of CD73-associated ecto-5-nucleotidase. Moreover, addition of 5-AMP to HGF resulted in the elevation of cyclic adenosine monophosphate (cAMP). Flow cytometric analysis revealed that ecto-ADA expression on HGF could be increased by pretreatment with exogenous ADA. However, this maximum expression of ecto-ADA did not lead to a significant increase in metabolism of exogenously added extracellular Ado. Interestingly, however, the cAMP response to Ado generated from 5-AMP via CD73 was significantly decreased by the pretreatment of HGF with exogenous ADA and this inhibitory effect was reversed by the specific ADA inihibitor 2-deoxycoformycin. These results suggest that ecto-ADA, which can be anchored to CD26 on HGF, has the potential to metabolize CD73-generated Ado in the microenvironmental milieu and that this plays a critical role in the regulation of AdoR activation.
日本炎症・再生医学会の論文
2005-05-25