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PI3K/Akt signaling pathway controls PGE 2 ‐induced ICAM‐1 expression through activation of NF‐kB
Author(s) -
Park Tae yeop,
Jung YiSook,
Baik Eun Joo,
Moon ChangHyun,
Lee Soo Hwan
Publication year - 2010
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.24.1_supplement.590.8
Subject(s) - pi3k/akt/mtor pathway , ly294002 , protein kinase b , phosphorylation , chemistry , nf κb , prostaglandin e , signal transduction , microbiology and biotechnology , inflammation , medicine , biology , biochemistry
Prostaglandin E 2 (PGE 2 ) is known to be the principal pro‐inflammatory prostanoid and play important roles in brain disease through binding to four G protein‐coupled receptor(EP1‐4). However, there have been contradictory reports on its actions in inflammation processes. For instance, PGE 2 inhibits or stimulates ICAM‐1 expression depending on the cell type and experimental conditions. In the present study, we investigated whether EP receptor‐mediated elevation of cAMP is necessary for the effect of PGE 2 on ICAM‐1 expression in bEnd.3 cerebrovascular cells. PGE 2 as well as dbcAMP and forskolin stimulated ICAM‐1 expression, and induced PI3K‐dependent Akt phosphorylation. LY294002, a PI3K inhibitor, attenuated PGE 2 ‐induced ICAM‐1 expression indicating possible involvement of PI3K in PGE 2 ‐induced ICAM‐1 expression. This inference was further supported by the separate experiment using constitutively active and dominant negative Akt constructs. NF‐κB inhibitors such as BAY‐11 and MG‐132 diminished the PGE 2 ‐induced ICAM‐1 expression implicating the role of NF‐κB. This result was further supported by increases in the IκB phosphorylation, translocation of NF‐κB into nucleus and the activity of NF‐κB‐responsive promoter construct. Interestingly, ectopic expression of dominant negative Akt resulted in the reduction of PGE 2 ‐induced IκB phosphorylation. Taken together, these results suggest that PGE 2 ‐induced ICAM‐1 expression is mediated by PI3K‐dependent NF‐κB activation. This study was supported by grants from Ajou University School of Medicine and Gyunggi‐do through CCRB‐GRRC