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Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model.
MedLine Citation:
PMID:  23137705     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Monocytes and factor Xa (FXa) are procoagulant agents implicated in the physio-pathological 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 TF mRNA 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.
Authors:
Sonia Ben-Hadj-Khalifa; Philippe Nguyen; Touhami Mahjoub; Nathalie Hézard
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  European cytokine network     Volume:  -     ISSN:  1952-4005     ISO Abbreviation:  Eur. Cytokine Netw.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100879     Medline TA:  Eur Cytokine Netw     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Unité de recherche des maladies hématologiques et auto-immunes, faculté de pharmacie, 5000 Monastir, Tunisie, Laboratoire d'hématologie, CHU Robert Debré, 51092 Reims Cedex, France.
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