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首页> 外文期刊>Journal of Cellular Physiology >Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells
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Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells

机译:腺苷酸调节促炎的信号凝血酶在内皮细胞的功能

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The plasma level of the regulatory metabolite adenosine increases during the activation of coagulation and inflammation. Here we investigated the effect of adenosine on modulation of thrombin-mediated proinflammatory responses in HUVECs. We found that adenosine inhibits the barrier-disruptive effect of thrombin in HUVECs by a concentration-dependent manner. Analysis of cell surface expression of adenosine receptors revealed that A2A and A2B are expressed at the highest level among the four receptor subtypes (A2BA2AA1A3) on HUVECs. The barrier-protective effect of adenosine in response to thrombin was recapitulated by the A2A specific agonist, CGS 21680, and abrogated both by the siRNA knockdown of the A2A receptor and by the A2A-specific antagonists, ZM-241385 and SCH-58261. The thrombin-induced RhoA activation and its membrane translocation were both inhibited by adenosine in a cAMP-dependent manner, providing a molecular mechanism through which adenosine exerts a barrier-protective function. Adenosine also inhibited thrombin-mediated activation of NF-κB and decreased adhesion of monocytic THP-1 cells to stimulated HUVECs via down-regulation of expression of cell surface adhesion molecules, VCAM-1, ICAM-1, and E-selectin. Moreover, adenosine inhibited thrombin-induced elevated expression of proinflammatory cytokines, IL-6 and HMGB-1; and chemokines, MCP-1, CXCL-1, and CXCL-3. Taken together, these results suggest that adenosine may inhibit thrombin-mediated proinflammatory signaling responses, thereby protecting the endothelium from injury during activation of coagulation and inflammation.
机译:等离子体水平的监管代谢物在激活腺苷增加凝血和炎症。调查了腺苷的影响调制的thrombin-mediated促炎在HUVECs反应。抑制的barrier-disruptive效果凝血酶在HUVECs浓度的方式。腺苷酸受体透露,负责和A2B在四个表示在最高水平受体亚型(A2B A2A A1 A3)HUVECs。腺苷对凝血酶研究生院理事会,负责完成的特定受体激动剂21680年,废除的siRNA击倒负责的受体和A2A-specific拮抗剂,zm评选- 241385和原理图- 58261。thrombin-induced RhoA激活及其膜易位都由腺苷抑制cAMP-dependent的方式,提供一个分子腺苷是一种机制barrier-protective函数。抑制NF -κB thrombin-mediated激活和单核细胞的粘附降低THP-1细胞通过下调的刺激HUVECs的细胞表面粘附分子的表达,VCAM-1、ICAM-1 E-selectin。腺苷抑制thrombin-induced升高促炎细胞因子的表达,il - 6和HMGB-1;CXCL-3。腺苷酸可以抑制thrombin-mediated促炎反应信号,从而保护内皮细胞在损伤激活凝血和炎症。

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