Casein-derived tripeptide, Val-Pro-Pro (VPP), modulates monocyte adhesion to vascular endothelium.
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.
Aihara
Kotaro
K
Functional Food and Drink Development Laboratory, Calpis Co., Ltd, Japan.
Ishii
Hideto
H
Yoshida
Masayuki
M
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
D002364:Caseins; D009842:Oligopeptides; C489031:valyl-prolyl-proline; D048670:MAP Kinase Kinase 4; D013755:Tetradecanoylphorbol Acetate