D609, a phosphatidylcholine-specific phospholipase C inhibitor, blocks interleukin-1 beta-induced vascular cell adhesion molecule 1 gene expression in human endothelial cells.
At sites of inflammation, endothelial cells play a major role in defining the types of leukocytes that are recruited to a specific area. This is accomplished, at least in part, through the cytokine induction of cell surface adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1). We investigated the role of phosphatidylcholine-specific phospholipase C in the induction of VCAM-1 gene expression by interleukin-1 beta. D609, a phosphatidylcholine-specific phospholipase C inhibitor, reduced VCAM-1 cell surface expression and VCAM-1 promoter activity in human endothelial cells in a dose-dependent manner. D609 did not affect nuclear translocation of nuclear factor-kappa B but inhibited nuclear factor-kappa B-mediated transcription. The results of this study indicate that phosphatidylcholine-specific phospholipase C is required for activation of nuclear factor-kappa B and cytokine induction of VCAM-1 gene expression in endothelial cells.
Cobb
R R
RR
Biology Department, Tanabe Research Laboratories, San Diego, California 92121, USA.
Felts
K A
KA
Parry
G C
GC
Mackman
N
N
D001483:Base Sequence; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009636:Norbornanes; D011401:Promoter Regions, Genetic; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D001952:Bridged-Ring Compounds; D007375:Interleukin-1; D016328:NF-kappa B; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; D019010:Vascular Cell Adhesion Molecule-1; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases