PMID- 15921025
OWN - NLM
STAT- MEDLINE
DCOM- 20050919
LR  - 20171116
IS  - 0378-6501 (Print)
IS  - 0378-6501 (Linking)
VI  - 31
IP  - 1
DP  - 2005
TI  - Nifedipine inhibits tumor necrosis factor-alpha-induced upregulation of monocyte 
      chemoattractant protein-1 mRNA levels by suppressing CD40 expression in 
      endothelial cells.
PG  - 13-7
AB  - There is a growing body of evidence that dihydropyridine-based calcium 
      antagonists (DHPs) improve endothelial function, thus slowing the development and 
      progression of atherosclerosis. We have previously shown that nifedipine, one of 
      the most popular DHPs, inhibits tumor necrosis factor-alpha (TNF-alpha)-induced 
      reactive oxygen species generation and subsequent monocyte chemoattractant 
      protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVEC). 
      However, the molecular mechanism underlying this phenomenon remains to be 
      elucidated. CD40, a cell surface receptor that belongs to TNF-alpha receptor, has 
      been associated with the pathogenesis of chronic inflammatory diseases such as 
      atherosclerosis. In this study, we investigated the involvement of CD40 in MCP-1 
      suppression by nifedipine in TNF-alpha-exposed HUVEC. Nifedipine completely 
      inhibited TNF-alpha-induced upregulation of CD40 mRNA levels in HUVEC. 
      Furthermore, antibody against human CD40 was found to significantly inhibit 
      upregulation of MCP-1 mRNA levels in TNF-alpha-exposed HUVEC. These results 
      demonstrate that nifedipine could inhibit the TNF-alpha-induced upregulation of 
      MCP-1 mRNA levels via suppression of CD40 expression in HUVEC. Our present study 
      suggests that blockade of CD40 signaling in endothelial cells may be a molecular 
      target for the vasculoprotective property of nifedipine.
FAU - Yamagishi, S
AU  - Yamagishi S
AD  - Department of Medicine, Kurume University School of Medicine, Kurume, Japan. 
      shoichi@med.kurume-u.ac.jp
FAU - Takeuchi, M
AU  - Takeuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Drugs Exp Clin Res
JT  - Drugs under experimental and clinical research
JID - 7802135
RN  - 0 (CD40 Antigens)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - CD40 Antigens/*biosynthesis/genetics
MH  - Calcium Channel Blockers/*pharmacology
MH  - Chemokine CCL2/*biosynthesis
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Nifedipine/*pharmacology
MH  - RNA, Messenger/antagonists & inhibitors/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Umbilical Veins/cytology
MH  - Up-Regulation
EDAT- 2005/06/01 09:00
MHDA- 2005/09/20 09:00
CRDT- 2005/06/01 09:00
PHST- 2005/06/01 09:00 [pubmed]
PHST- 2005/09/20 09:00 [medline]
PHST- 2005/06/01 09:00 [entrez]
PST - ppublish
SO  - Drugs Exp Clin Res. 2005;31(1):13-7.