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-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 αLipoic 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.
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy.
Veronica
V
Tisato
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/01, 34137 Trieste, Italy.
Giorgio
G
Zauli
Department of Life Sciences, University of Trieste, Via Manzoni 16, 34137 Trieste, Italy.
Erika
E
Rimondi
Vascular Disease Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy.
Sergio
S
Gianesini
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy.
Laura
L
Brunelli
Vascular Disease Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy.
Erica
E
Menegatti
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy ; Vascular Disease Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy.
Paolo
P
Zamboni
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy.
Paola
P
Secchiero
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D010750:Phosphoproteins; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D008063:Thioctic Acid; D048051:p38 Mitogen-Activated Protein Kinases