Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University, Tübingen, Germany.
J Immunol. 2011 Jan 1;186(1):549-55. doi: 10.4049/jimmunol.1002671. Epub 2010 Nov 22.
Previous studies implicated the anti-inflammatory potential of the adenosine 2B receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is limited by its very short t(1/2). To further define alternative adenosine signaling, we examined the role of netrin-1 during acute inflammatory peritonitis. In this article, we report that animals with endogenous repression of netrin-1 (Ntn1(+/-)) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological changes compared with controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly decreased i.p. inflammatory changes. This effect was not present in animals with deletion of A2BAR (A2BAR(-/-)). A2BAR(-/-) animals demonstrated no change in cell count, i.p. cytokine concentration, or histology in response to netrin-1 injection. These data strengthen the role of netrin-1 as an immunomodulatory protein exerting its function in dependence of the A2BAR and further define alternative adenosine receptor signaling.
先前的研究表明，腺苷 2B 受体（A2BAR）具有抗炎潜力。A2BAR 的激活是通过腺苷实现的，但由于其半衰期非常短而受到限制。为了进一步确定替代的腺苷信号通路，我们研究了轴突导向因子 1（netrin-1）在急性炎症性腹膜炎中的作用。在本文中，我们报告称，与对照组相比，内源性抑制 netrin-1（Ntn1(+/-)）的动物在酵母聚糖 A 腹膜炎模型中表现出更高的细胞计数、更高的腹腔细胞因子浓度和更明显的组织学变化。外源性 netrin-1 可显著降低腹腔内的炎症变化。在 A2BAR 缺失（A2BAR(-/-)）的动物中，这种作用不存在。A2BAR(-/-)动物对 netrin-1 注射没有反应，细胞计数、腹腔细胞因子浓度或组织学没有变化。这些数据进一步证实了 netrin-1 作为一种免疫调节蛋白的作用，其功能依赖于 A2BAR，并进一步定义了替代的腺苷受体信号通路。
