[en] BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. METHODS: In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-alpha, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test. RESULTS: Pretreatment of the animals with PACs (10, 30 and 60 mg/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. CONCLUSION: This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-alpha-induced VEGF transcription.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Garbacki, Nancy ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Kinet, Marie
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Damas, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Proanthocyanidins, from Ribes Nigrum Leaves, Reduce Endothelial Adhesion Molecules Icam-1 and Vcam-1
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