Protease-Activated Receptor 1 Enhances Poly I:C Induction of the Antiviral Response in Macrophages and Mice.
Protease-Activated Receptor 1 Enhances Poly I:C Induction of the Antiviral Response in Macrophages and Mice.
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DOI：
10.1159/000450853
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发表时间：
2017
影响因子：
5.3
通讯作者：
Mackman N
中科院分区：
文献类型：
--
作者：
Antoniak S;Tatsumi K;Bode M;Vanja S;Williams JC;Mackman N
凝血级联在病毒感染期间被激活，作为宿主防御系统的一部分。凝血蛋白酶通过蛋白酶激活受体（PAR）的裂解来激活细胞。最近，我们报道了PAR-1的激活增强了心脏成纤维细胞和柯萨奇病毒B3感染小鼠心脏中干扰素（IFN）-β和CXCL 10的表达。在这项研究中，我们使用的双链RNA模拟聚肌苷酸：聚胞苷酸（聚I：C）诱导巨噬细胞和小鼠的抗病毒反应。PAR-1的激活增强了poly I：C对小鼠巨噬细胞系RAW 264.7、骨髓源性小鼠巨噬细胞（BMM）和小鼠脾细胞中IFNβ和CXCL 10表达的诱导。接下来，使用poly I：C在野生型（WT）和PAR-1−/−小鼠的脾脏和血浆中诱导I型IFN先天免疫应答。我们发现，与WT小鼠相比，poly I：C处理的PAR-1−/−小鼠和给予凝血酶抑制剂达比加群酯的WT小鼠在脾脏和血浆中的IFNβ和CXCL 10表达显著降低。这些研究表明，凝血酶激活PAR 1有助于小鼠的抗病毒反应。
The coagulation cascade is activated during viral infections as part of the host defense system. Coagulation proteases activate cells by cleavage of protease-activated receptors (PAR). Recently, we reported that activation of PAR-1enhanced interferon (IFN)-β and CXCL10 expression in cardiac fibroblasts and in the hearts of mice infected with Coxsackievirus B3. In this study, we used the double-stranded RNA mimetic polyinosinic:polycytidylic acid (poly I:C) to induce an anti-viral response in macrophages and mice. Activation of PAR-1 enhanced poly I:C induction of IFNβ and CXCL10 expression in the murine macrophage cell line RAW264.7, bone-marrow derived mouse macrophages (BMM) and mouse splenocytes. Next, poly I:C was used to induce a type I IFN innate immune response in the spleen and plasma of wild-type (WT) and PAR-1−/− mice. We found that poly I:C treated PAR-1−/− mice and WT mice given the thrombin inhibitor dabigatran etexilate exhibited significantly less IFNβ and CXCL10 expression in the spleen and plasma compared to WT mice. These studies suggest that thrombin activation of PAR1 contributes to the anti-viral response in mice.