Anti-inflammatory preconditioning by agonists of adenosine A1 receptor.
Anti-inflammatory preconditioning by agonists of adenosine A1 receptor.
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腺苷A1受体激动剂的抗炎预处理。
DOI：
10.1371/journal.pone.0002107
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发表时间：
2008-05-07
期刊：
影响因子：
3.7
通讯作者：
Douvdevani A
中科院分区：
文献类型：
--
作者：
Nakav S;Chaimovitz C;Sufaro Y;Lewis EC;Shaked G;Czeiger D;Zlotnik M;Douvdevani A
腺苷水平在炎症过程中升高，并通过与四种不同的G蛋白偶联受体结合来调节炎症反应。提示腺苷通过其A1受体（A1 R）发挥促炎作用，通过其A2 A受体（A2 AR）发挥抗炎作用。因此，了解腺苷受体调节的机制可能会促进各种炎症性疾病的治疗。我们以前报道过，在白细胞募集过程中A1 R表达达到峰值，随后在炎症消退过程中A2 AR达到峰值。在这里，我们研究了A1 R激活是否依次诱导A2 AR表达，并通过此逆转炎症。在体外培养的腹腔巨噬细胞（PMΦ）和原代腹膜间皮细胞（PMC）中检测腺苷对A1 R介导的A2 AR表达的影响。百日咳毒素（PTX）可抑制A2 AR的诱导，并部分依赖于A2 AR的刺激。给予健康小鼠A1 R激动剂可降低PMC中A1 R表达并诱导A2 AR产生。在E.大肠杆菌接种后血清TNFα和IL-6水平降低，白细胞募集减少。A1 R拮抗剂预处理以及A2 AR拮抗剂后期处理可阻断预处理，A2 AR −/−小鼠中不存在预处理。我们的数据表明，A1受体激动剂预处理通过诱导A2 AR的产生来促进炎症的消退。未来的意义可能包括在炎症性疾病期间的早期治疗或在预期的高风险炎症事件之前的预处理，例如侵入性手术和器官移植。
Adenosine levels rise during inflammation and modulate inflammatory responses by engaging with four different G protein-coupled receptors. It is suggested that adenosine exhibits pro-inflammatory effects through its A1 receptor (A1R), and anti-inflammatory effects through A2A receptor (A2AR). Therefore, understanding of the mechanisms that govern adenosine receptor regulation may advance treatment of various inflammatory disorders. We previously reported that peak A1R expression during leukocyte recruitment, is followed by a peak in A2AR during inflammation resolution. Here, we examined whether A1R activation sequentially induces A2AR expression and by this reverses inflammation. The effect of adenosine on A1R mediated A2AR expression was examined in peritoneal macrophages (PMΦ) and primary peritoneal mesothelial cells (PMC) in vitro. Induction of A2AR was inhibited by pertussis toxin (PTX) and partly dependent on A2AR stimulation. Administration of A1R agonists to healthy mice reduced A1R expression and induced A2AR production in PMC. Mice that were preconditioned with A1R agonists 24 hours before E. coli inoculation exhibited decreased TNFα and IL-6 sera levels and reduced leukocytes recruitment. Preconditioning was blocked by pretreatment with A1R antagonist, as well as, or by late treatment with A2AR antagonist, and was absent in A2AR−/− mice. Our data suggest that preconditioning by an A1R-agonist promotes the resolution of inflammation by inducing the production of A2AR. Future implications may include early treatment during inflammatory disorders or pretreatment before anticipated high risk inflammatory events, such as invasive surgery and organ transplantation.
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影响因子：
19.6
作者：
STYLIANOU, E;JENNER, LA;WILLIAMS, JD
通讯作者：
WILLIAMS, JD
影响因子：
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作者：
Rogachev, B.;Ziv, N. Y.;Douvdevani, A.
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Mazar, J;Rogachev, B;Douvdevani, A
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McColl, SR;St-Onge, M;Pouliot, M
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Pouliot, M
影响因子：
19.6
作者：
DOUVDEVANI, A;RAPOPORT, J;CHAIMOVITZ, C
通讯作者：
CHAIMOVITZ, C