title: Casein-derived tripeptide, Val-Pro-Pro (VPP), modulates monocyte adhesion to vascular endothelium.
abstract: OBJECTIVE
  A food-derived bioactive tripeptide, Val-Pro-Pro (VPP), has been shown to possess angiotensin I-converting enzyme (ACE) inhibitory activity and foods containing such peptides exhibit an anti-hypertensive effect in clinical settings.
  
  
  METHODS
  The present study focused on the effect of VPP on monocyte adhesion to endothelium under flow conditions using phorbol 12-myristate 13-acetate (PMA)-stimulated monocytic THP-1 cells.
  
  
  RESULTS
  Pre-incubation of THP-1 cells with VPP (1 mM, 24 hours) significantly decreased the PMA-induced adhesion of THP-1 cells (p<0.05) to human umbilical vein endothelial cells (HUVECs). PMA-induced up-regulation of beta1 and beta2 integrin activation in THP-1 cells was downregulated by VPP, which significantly suppressed only the PMA-induced phosphorylation of JNK (p<0.05) in THP-1 cells. In addition, preincubation of THP-1 with SP600125, a specific inhibitor of JNK, resulted in significant reduction of the PMA-induced adhesion of THP-1. Interestingly, another tripeptide with comparable ACE inhibitory activity, Leu-Gly-Pro (LGP), failed to reduce the PMA-induced adhesion of THP-1, suggesting a distinct anti-inflammatory effect of VPP on THP-1 adhesion.
  
  
  CONCLUSIONS
  These observations suggest that VPP moderates monocyte adhesion to inflamed endothelia via attenuation of the JNK pathway in monocytes, which might contribute to the primary prevention of atherosclerosis.
authors.affiliation: Functional Food and Drink Development Laboratory, Calpis Co., Ltd, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Aihara
authors.forename: Hideto
authors.initials: H
authors.lastname: Ishii
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D002364:Caseins / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002364:Caseins; D009842:Oligopeptides; C489031:valyl-prolyl-proline; D048670:MAP Kinase Kinase 4; D013755:Tetradecanoylphorbol Acetate