Enhancement of activated β₁-integrin expression by prostaglandin E₂ via EP receptors in isolated human coronary arterial endothelial cells: implication for the treatment of Kawasaki disease

Abstract.

Objective:

Plasma prostaglandin E₂ (PGE₂) levels are markedly elevated in acute Kawasaki disease (KD). We evaluated the function of the EP receptors in the expression of activated β₁-integrin stimulated by PGE₂ in human coronary arterial endothelial cells (HCAEC).

Methods:

We determined the mRNA expression of the PGE₂ 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 β₁-integrin stimulated by PGE₂ 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 EP₁, EP₂ and EP₃ expression in HCAEC. The EP₂ and EP₃ agonists enhanced the expression of activated β₁-integrin in HCAEC. The potency of the EP₂ agonist was significantly greater than that of the EP₃ agonist. Pretreatment with the EP₁, EP₂ and EP₃ antagonists inhibited the expression of activated β₁-integrin induced by PGE₂ in HCAEC. The potency of the EP₂ antagonist was significantly greater than that of the EP₁ and EP₃ antagonists.

Conclusions:

Our results suggest that PGE₂ mainly induces the activation of β₁-integrins via the EP₂ receptor in HCAEC. Our results further suggest that the EP₂ antagonist modulates the inflammatory response during KD vasculitis.