No abstract

Increased leukocyte adhesion and infiltration under various pathological conditions is accompanied by increased expression of endothelial ICAM‐1 and the blockade of ICAM‐1 ligation limits leukocyte infiltration and brain damage. PGE2 is known to be the principal pro‐inflammatory prostanoid and play important roles in brain diseases through binding to EP1‐4 receptors. However, there have been contradictory reports on its actions during inflammation processes, especially in vascular endothelial cells. In this study, we investigated the roles of PGE2 in the expression of ICAM‐1 in bEnd.3 cells and therein involved signaling pathways. We investigated that elevation of cAMP is necessary for PGE2‐induced ICAM‐1 expression in bEnd.3 cells. We determined effect of PGE2 on Epac activation using Rap1‐GTP pull down assay and effect of Epac on PI3K/Akt activation as well as ICAM‐1 expression. Next, we showed that loss of Akt activity results in inhibition of PGE2‐induced NF‐κB activation. On the other hand, interestingly enough, PKA inhibitor stimulated Akt phosphorylation and ICAM‐1 expression and specific activator inhibited PGE2‐induced ICAM‐1 expression and Akt phosphorylation. Taken together, these data suggest that this antagonism between PKA and Epac signaling is importantly involved in the regulation of PI3K/Akt signaling axis, and thereby ICAM‐1 expression in cerebrovascular endothelial cells.This study was supported by grants from Ajou University School of Medicine and Gyunggi‐do through CCRB‐GRRC