Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury.
Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury.
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DOI：
10.1016/j.exphem.2009.02.001
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发表时间：
2009-05
影响因子：
2.6
通讯作者：
Ravid K
中科院分区：
文献类型：
--
作者：
Chen H;Yang D;Carroll SH;Eltzschig HK;Ravid K
肿瘤坏死因子-α（TNF-α）表达的控制影响应激反应期间的各种过程。巨噬细胞是TNF-α的主要来源，已知其水平受腺苷调节。以前的研究强调了A2 a腺苷受体（A2 aAR）在这一过程中的作用，而A2 b腺苷受体（A2 bAR）的作用尚未明确确定。在这里，我们研究了A2 bAR在基线和血管应激下对巨噬细胞调节TNF-α的作用。我们采用了较新的A2 bAR选择性配体BAY 60-6583体外和体内，和A2 bAR拮抗剂CVT-6883，以及检查来自对照或A2 bAR敲除（KO）小鼠的巨噬细胞。我们发现，A2 bAR的表达在来自动脉损伤的野生型小鼠的巨噬细胞中上调，并且这种受体活性控制从巨噬细胞释放的TNF-α的水平。我们发现A2 bAR在调节TNF-α中起重要作用，这可能有助于腺苷在血管应激下的抗炎作用。这一结论可以将注意力集中在该受体作为治疗靶点上。
The control of expression of Tumor Necrosis Factor-alpha (TNF-α) impacts a variety of processes during a stress response. Macrophages are a major source of TNF-α, the level of which is known to be regulated by adenosine. Previous studies highlighted the role of the A2a adenosine receptor (A2aAR) 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-α regulation by macrophages at base line 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 (KO) 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-α released from macrophages. We identified a significant role for the A2bAR in the regulation TNF-α, 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.
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DOI：
10.1016/j.bbrc.2008.07.059
发表时间：
2008-10-24
影响因子：
3.1
作者：
Hilaire, Cynthia St.;Koupenova, Milka;Carroll, Shannon H.;Smith, Barbara D.;Ravid, Katya
通讯作者：
Ravid, Katya
影响因子：
4.9
作者：
Aringer M;Smolen JS
通讯作者：
Smolen JS
影响因子：
7.3
作者：
Sitkovsky, M.;Lukashev, D.;Ohta, A.
通讯作者：
Ohta, A.
影响因子：
15.9
作者：
Yang, Dan;Zhang, Ying;Ravid, Katya
通讯作者：
Ravid, Katya
影响因子：
4
作者：
Hilaire, Cynthia St.;Yang, Dan;Ravid, Katya
通讯作者：
Ravid, Katya