Nifedipine inhibits tumor necrosis factor-alpha-induced leukocyte adhesion to endothelial cells by suppressing vascular cell adhesion molecule-1 (VCAM-1) expression.
We have previously shown that nifedipine, one of the most popular dihydropyridine-based calcium antagonists (DHPs), blocked tumor necrosis factor-alpha (TNF-alpha)-induced reactive oxygen species generation and subsequent monocyte chemoattractant protein-1 expression in endothelial cells (ECs), thus suggesting that nifedipine may inhibit monocyte recruitment, an initiating step in atherosclerosis. However, the effect of nifedipine on leukocyte adhesion to ECs, another pivotal step in the early stage of atherosclerosis, remains to be elucidated. In this study, we investigated whether nifedipine could inhibit TNF-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) expression and subsequent leukocyte adhesion to human umbilical vein endothelial cells (HUVEC). Nifedipine significantly inhibited TNF-alpha-induced up-regulation of VCAM-1 mRNA levels in HUVEC. Furthermore, nifedipine was found to block MOLT-3 (a human lymphoblastic cell line) cell adhesion to TNF-alpha-exposed HUVEC. The results suggest that nifedipine could inhibit TNF-alpha-induced leukocyte adhesion to ECs by suppressing VCAM-1 expression. Our present study provides a novel beneficial aspect of nifedipine on atherogenesis.
Yamagishi
S
S
Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Takeuchi
M
M
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D009543:Nifedipine