Resveratrol, a polyphenolic phytostilbene, inhibits endothelial monocyte chemotactic protein-1 synthesis and secretion.
OBJECTIVE
Resveratrol is a naturally occurring polyphenol phytoestrogen and one of several constituents of red wine thought to be cardioprotective. We investigated the effect of resveratrol on the expression of the atherogenic chemokine, monocyte chemotactic protein-1 (MCP-1).


METHODS
Human umbilical vein endothelial cells were stimulated with interleukin-1beta (IL-1beta) in the absence or presence of resveratrol. MCP-1 levels were determined by ELISA and MCP-1 mRNA was measured.


RESULTS
Resveratrol (1-100 microM) dose-dependently inhibited IL-1beta-stimulated MCP-1 secretion, with approximately 45% inhibition at 50 microM resveratrol. This was a Gi-protein- and NO-dependent effect. Resveratrol also significantly inhibited MCP-1 gene expression in a Gi-protein-dependent but NO-independent manner. While resveratrol had no effect on MCP-1 mRNA degradation, it inhibited MCP-1 promoter activity and reduced nuclear factor kappaB and activator protein-1 binding activity induced by IL-1beta. Moreover, while hemoxygenase-1 (HO-1) expression was induced by resveratrol in human umbilical vein endothelial cells, neither treatment with the HO-1 inhibitor tin-protoporphyrin IX nor siRNA-directed knockdown of HO-1 had any effect on the inhibition of MCP-1 mRNA or protein secretion by resveratrol.


CONCLUSIONS
These data demonstrate an inhibitory effect of resveratrol on MCP-1 synthesis and secretion, mediated via distinct signaling pathways. The inhibition of MCP-1 may represent a novel cardioprotective mechanism of resveratrol.
Cullen
John P
JP
Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, N.Y. 14642, USA.
Morrow
David
D
Jin
Ying
Y
Curley
Brian
B
Robinson
Alex
A
Sitzmann
James V
JV
Cahill
Paul A
PA
Redmond
Eileen M
EM
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D012264:Ribonucleotide Reductases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000077185:Resveratrol