Chen Hongjie, Yang Dan, Carroll Shannon H, Eltzschig Holger K, Ravid Katya
Department of Biochemistry, Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass., USA.
Exp Hematol. 2009 May;37(5):533-8. doi: 10.1016/j.exphem.2009.02.001.
The control of expression of tumor necrosis factor-alpha (TNF-alpha) impacts a variety of processes during a stress response. Macrophages are a major source of TNF-alpha, the level of which is known to be regulated by adenosine. Previous studies highlighted the role of the A2a adenosine receptor in this process, while the role of the A2b adenosine receptor (A2bAR) has not been clearly identified. Here, we examined the contribution of the A2bAR to TNF-alpha regulation by macrophages at baseline and under vascular stress.
We employed a newer A2bAR-selective ligand, BAY 60-6583 in vitro and in vivo, and an A2bAR antagonist CVT-6883, as well as examined macrophages derived from control or A2bAR knockout mice.
We found that the expression of the A2bAR is upregulated in macrophages derived from wild-type mice subjected to arterial injury, and this receptor activity controls the level of TNF-alpha released from macrophages.
We identified a significant role for the A2bAR in the regulation of TNF-alpha, which would contribute to the anti-inflammatory actions of adenosine under vascular stress. This conclusion could focus attention on this receptor as a therapeutic target.
肿瘤坏死因子-α（TNF-α）表达的调控在应激反应过程中影响多种生理过程。巨噬细胞是TNF-α的主要来源，其水平已知受腺苷调节。先前的研究强调了A2a腺苷受体在此过程中的作用，而A2b腺苷受体（A2bAR）的作用尚未明确。在此，我们研究了A2bAR在基线和血管应激状态下对巨噬细胞调节TNF-α的贡献。
我们在体外和体内使用了一种新型的A2bAR选择性配体BAY 60-6583，以及一种A2bAR拮抗剂CVT-6883，并对来自对照或A2bAR基因敲除小鼠的巨噬细胞进行了检测。
我们发现，在经历动脉损伤的野生型小鼠来源的巨噬细胞中，A2bAR的表达上调，并且这种受体活性控制着巨噬细胞释放的TNF-α水平。
我们确定了A2bAR在TNF-α调节中的重要作用，这将有助于腺苷在血管应激状态下的抗炎作用。这一结论可能会使人们将注意力集中在该受体作为治疗靶点上。
