Enhancement of activated beta1-integrin expression by prostaglandin E2 via EP receptors in isolated human coronary arterial endothelial cells: implication for the treatment of Kawasaki disease.
OBJECTIVE
Plasma prostaglandin E(2) (PGE(2)) levels are markedly elevated in acute Kawasaki disease (KD). We evaluated the function of the EP receptors in the expression of activated beta(1)-integrin stimulated by PGE(2) in human coronary arterial endothelial cells (HCAEC).


METHODS
We determined the mRNA expression of the PGE(2) receptors, EP receptors (EP(1-4)) in HCAEC by RT-PCR and protein expression by Western blotting. We evaluated the function of the EP receptors in the expression of activated beta(1)-integrin stimulated by PGE(2) in HCAEC, using antagonists and agonists of the EP receptors, by flow cytometry.


RESULTS
RT-PCR revealed mRNAs for all four EP receptors in HCAEC. Western blotting demonstrated EP(1), EP(2) and EP(3) expression in HCAEC. The EP(2) and EP(3) agonists enhanced the expression of activated beta(1)-integrin in HCAEC. The potency of the EP(2) agonist was significantly greater than that of the EP(3) agonist. Pretreatment with the EP(1), EP(2) and EP(3) antagonists inhibited the expression of activated beta(1)-integrin induced by PGE(2) in HCAEC. The potency of the EP(2) antagonist was significantly greater than that of the EP(1) and EP(3) antagonists.


CONCLUSIONS
Our results suggest that PGE(2) mainly induces the activation of beta(1)-integrins via the EP(2) receptor in HCAEC. Our results further suggest that the EP(2) antagonist modulates the inflammatory response during KD vasculitis.
Kajimoto
M
M
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Ichiyama
T
T
Ueno
Y
Y
Shiraishi
M
M
Hasegawa
M
M
Furukawa
S
S
D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000628:therapy*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*
D019012:Integrin beta1; D020033:Protein Isoforms; D018078:Receptors, Prostaglandin E; D015232:Dinoprostone