Modification of cytokine milieu by A2A adenosine receptor signaling-possible application for inflammatory diseases
Modification of cytokine milieu by A2A adenosine receptor signaling-possible application for inflammatory diseases
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DOI：
10.1081/ncn-200027368
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发表时间：
2004-10-01
影响因子：
1.3
通讯作者：
Kumagai, S
中科院分区：
文献类型：
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作者：
Koshiba, M;Nakamachi, Y;Kumagai, S
A(2A)腺苷受体(A(2A)R)或β(2)肾上腺素能受体(ADR)(β(2)R)信号以浓度依赖的方式抑制脂多糖(LPS)刺激的人外周血CD14(+)细胞(PB-CD14)产生促炎细胞因子TNF-α(TNF-α)。这些抑制作用可能是通过细胞内cAMP的增加来实现的。A(2A)R激动剂和β(2)R激动剂对脂多糖刺激的PB-CD14细胞产生的肿瘤坏死因子有协同抑制作用。这些结果提示，细胞外腺苷的抗炎作用至少部分是通过A(2A)信号改变细胞因子环境，A(2A)R和β(2)R的靶向作用可能对炎症性疾病有很强的治疗潜力。
Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro lipopolysaccharide (LPS)-stimulated human peripheral blood CD14(+) cells (PB-CD14) was inhibited by A(2A) adenosine receptor (AdoR) (A(2A)R) or beta(2) adrenergic receptor (ADR) (beta(2)R) signaling in a concentration-dependent manner. These inhibitory effects were presumably mediated by the increase in intracellular cAMP. Furthermore A(2A)R agonist and beta(2)R agonist synergistically inhibited the TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the anti-inflammatory effect of extracellular adenosine is, at least in part, due to the modification of the cytokine milieu via A(2A) signaling, and that the targeting of both A(2A)R and beta(2)R may have strong therapeutic potential for the inflammatory diseases.