Platelet-activating factor-induced NF-κB activation enhances VEGF expression through a decrease in p53 activity

We investigated the role of p53 in nuclear factor (NF)-κB dependent, platelet-activating factor (PAF)-induced vascular endothelial growth factor (VEGF) expression. Transfected NF-κB subunits in ECV304 cells increased the tumor necrosis factor-α promoter activity, which was completely inhibited by p53. Transfected p53 increased p53RE promoter activity, which was completely inhibited by NF-κB subunits, indicating that cross-regulation occurs between NF-κB and p53. PAF-induced increase in VEGF expression was correlated with decreased p53 activity. These data suggest that NF-κB-dependency of the PAF-induced increase in VEGF expression is due to decreased p53 activity, which is reciprocally regulated by increased NF-κB activity.