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Antagonism between PKA and Epac signaling is involved in the regulation of PGE2‐induced ICAM‐1 expression in bEnd.3 cells
Author(s) -
Park Tae Yeop,
Lee Kwang Min,
Kim Jae Mi,
Jung Yi-Sook,
Baik Eun Joo,
Moon Chang-Hyun,
Lee Soo Hwan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.676.16
Subject(s) - protein kinase b , rap1 , microbiology and biotechnology , pi3k/akt/mtor pathway , icam 1 , signal transduction , chemistry , phosphorylation , activator (genetics) , inflammation , receptor , cancer research , biology , cell adhesion molecule , biochemistry , immunology
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. PGE 2 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 PGE 2 in the expression of ICAM‐1 in bEnd.3 cells and therein involved signaling pathways. We investigated that elevation of cAMP is necessary for PGE 2 ‐induced ICAM‐1 expression in bEnd.3 cells. We determined effect of PGE 2 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 PGE 2 ‐induced NF‐κB activation. On the other hand, interestingly enough, PKA inhibitor stimulated Akt phosphorylation and ICAM‐1 expression and specific activator inhibited PGE 2 ‐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