Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-in...

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Main Authors: Veronica Tisato, Giorgio Zauli, Erika Rimondi, Sergio Gianesini, Laura Brunelli, Erica Menegatti, Paolo Zamboni, Paola Secchiero
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/423407
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author Veronica Tisato
Giorgio Zauli
Erika Rimondi
Sergio Gianesini
Laura Brunelli
Erica Menegatti
Paolo Zamboni
Paola Secchiero
author_facet Veronica Tisato
Giorgio Zauli
Erika Rimondi
Sergio Gianesini
Laura Brunelli
Erica Menegatti
Paolo Zamboni
Paola Secchiero
author_sort Veronica Tisato
collection DOAJ
description Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n=31) in CVD patients’ plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that α-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.
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spelling doaj-art-1e7aa089a7884dde92e07658927044e92025-02-03T06:07:07ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/423407423407Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial CellsVeronica Tisato0Giorgio Zauli1Erika Rimondi2Sergio Gianesini3Laura Brunelli4Erica Menegatti5Paolo Zamboni6Paola Secchiero7Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/01, 34137 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via Manzoni 16, 34137 Trieste, ItalyVascular Disease Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, ItalyDepartment of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, ItalyVascular Disease Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, ItalyDepartment of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, ItalyDepartment of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, ItalyLarge vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n=31) in CVD patients’ plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that α-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.http://dx.doi.org/10.1155/2013/423407
spellingShingle Veronica Tisato
Giorgio Zauli
Erika Rimondi
Sergio Gianesini
Laura Brunelli
Erica Menegatti
Paolo Zamboni
Paola Secchiero
Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
Mediators of Inflammation
title Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
title_full Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
title_fullStr Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
title_full_unstemmed Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
title_short Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells
title_sort inhibitory effect of natural anti inflammatory compounds on cytokines released by chronic venous disease patient derived endothelial cells
url http://dx.doi.org/10.1155/2013/423407
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