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Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model.
European Cytokine Network ( IF 2.8 ) Pub Date : 2012-11-10 , DOI: 10.1684/ecn.2012.0315
Sonia Ben-Hadj-Khalifa 1 , Philippe Nguyen , Touhami Mahjoub , Nathalie Hézard
Affiliation  

BACKGROUND Monocytes and factor Xa (FXa) are procoagulant agents implicated in the physiopathological processes of atherosclerosis and thrombosis. OBJECTIVE we evaluated the anticoagulant effect of the anti-inflammatory cytokine IL-10 on an FXa-activated human monocyte (Hu-monocyte) procoagulant phenotype. METHODS Hu-monocytes were purified by elutriation and activated by FXa. The effect of IL-10 was assessed by means of a 2 h pre-incubation step with recombined human IL-10 (0.5 and 1 ng/mL). Real-time RT-PCR and Western blotting were used to evaluate the effect of IL-10 on tissue factor (TF) mRNA and protein synthesis. A thrombin generation (TG) assay was used as a functional test to assess the effect of IL-10 on TF-dependent TG. RESULTS we showed that IL-10 inhibited both TFmRNA and TF protein expression in a dose-dependant manner.We showed, as a functional consequence, that IL-10 inhibited Hu-monocyte-triggered TG and that this inhibition was concentration-dependant, and significant for all TG phases. The rate index of the propagation phase (rate index) was the most sensitive parameter while the endpoint of TG decay (S-tail) and the endogenous thrombin potential (ETP) were the least sensitive (inhibition of 80, 40 and 30% respectively). The IL-10 pattern of TG inhibition was similar to TF-Ab-induced inhibition: IC(50) were not reached by ETP and S-tail, and the lowest IC(50) values were reached by the rate index (0.61 ± 0.12 ng/mL and 1.87 ± 0.35 μg/mL respectively). CONCLUSION the anticoagulant effect of the anti-inflammatory cytokine IL-10 in an FXa-activated Hu-monocyte model is an additional illustration of the cross-talk between inflammation and coagulation, opening new approaches in the field of arteriosclerosis and thrombosis.

中文翻译:

在因子Xa激活的人类单核细胞模型中,抗炎细胞因子IL-10的抗凝特性。

背景技术单核细胞和Xa因子(FXa)是涉及动脉粥样硬化和血栓形成的生理病理过程的促凝血剂。目的我们评估了抗炎细胞因子IL-10对FXa激活的人单核细胞(Hu-monocyte)促凝表型的抗凝作用。方法通过淘洗纯化单核细胞,并通过FXa激活。通过与重组人IL-10(0.5和1 ng / mL)的2 h预温育步骤评估IL-10的作用。实时RT-PCR和蛋白质印迹用于评估IL-10对组织因子(TF)mRNA和蛋白质合成的影响。凝血酶生成(TG)分析用作功能测试,以评估IL-10对TF依赖性TG的影响。结果表明,IL-10以剂量依赖性方式抑制TFmRNA和TF蛋白的表达。作为功​​能性结果,IL-10抑制了Hu单核细胞触发的TG,并且这种抑制是浓度依赖性的,并且对于所有TG相均很重要。繁殖期的速率指数(速率指数)是最敏感的参数,而TG衰减的终点(S-tail)和内源性凝血酶电位(ETP)最不敏感(抑制率分别为80%,40%和30%) 。TG抑制的IL-10模式类似于TF-Ab诱导的抑制:ETP和S-tail未达到IC(50),速率指数达到最低IC(50)(0.61±0.12) ng / mL和1.87±0.35μg/ mL)。结论抗炎细胞因子IL-10在FXa激活的Hu单核细胞模型中的抗凝作用进一步说明了炎症与凝血之间的相互影响,
更新日期:2019-11-01
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