title: Resveratrol inhibits monocytic cell chemotaxis to MCP-1 and prevents spontaneous endothelial cell migration through Rho kinase-dependent mechanism.
abstract: OBJECTIVE
  Inflammatory cell recruitment and intimal neovascularization contribute to atherosclerotic plaque destabilization. The anti-inflammatory red wine polyphenol, resveratrol, has been implicated in cardiovascular protection. In this study, we investigated the effects of resveratrol on endothelial and monocytic cell migration.
  
  
  METHODS
  Human umbilical vein endothelial cell (EC) migration was assessed in a modified barrier assay. Chemotaxis of THP-1 monocytic cells towards monocyte chemoattractant protein (MCP)-1 was determined using a Boyden chamber. Erk phosphorylation downstream of MCP-1 receptor and activation of myosin phosphatase targeting subunit 1 (pMYPT1) downstream of Rho kinase were determined by Western blotting.
  
  
  RESULTS
  In resveratrol-treated cells, progressive shape elongation was observed, evident after 6h of treatment. Treatment with resveratrol (1-20 µmol/L) dose-dependently inhibited EC migration. This effect of resveratrol was independent of nuclear factor (NF)-kappaB and sirtuin 1, but was abrogated in the presence of Rho kinase inhibitors. Moreover, resveratrol induced pMYPT1 activation, indicating a novel mechanism of resveratrol activity in EC. In monocytic cells, treatment with resveratrol significantly inhibited chemotaxis towards MCP-1 already at 1 µmol/L. At a resveratrol concentration of 10 µmol/L, chemotaxis was reduced nearly to the negative control (unstimulated with MCP-1) levels. This effect was independent of NF-kappaB and RhoA signaling. In resveratrol treated monocytic cells, MCP-1-induced Erk phosphorylation downstream of CCR2 receptor was dose-dependently inhibited, as observed by Western blot analysis.
  
  
  CONCLUSIONS
  Resveratrol dose-dependently inhibited endothelial cell migration and MCP-1-induced monocytic cell chemotaxis. This activity may contribute to the cardioprotective effects of resveratrol by inhibition of intimal neovascularization and monocyte recruitment into the artery wall.
authors: Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Erlangen, Germany. Iwona_Cicha@yahoo.com
authors: Iwona
authors: I
authors: Cicha
authors: Melanie
authors: M
authors: Regler
authors: Katharina
authors: K
authors: Urschel
authors: Margarete
authors: M
authors: Goppelt-Struebe
authors: Werner G
authors: WG
authors: Daniel
authors: Christoph D
authors: CD
authors: Garlichs
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D013267:Stilbenes; D054460:rho-Associated Kinases; D000077185:Resveratrol