Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model.
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Date publication
juillet 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NGUYEN Philippe
Tous les auteurs :
Ben-Hadj-Khalifa S, Nguyen P, Mahjoub T, Hezard N
Lien Pubmed
Résumé
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 mug/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.
Référence
Eur Cytokine Netw. 2012 Jul-Sep;23(3):87-92.