Unique Regulation Profile of Prostaglandin E₁ on Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells

In the present study, we examined the effects of prostaglandin E ₁ (PGE₁) on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on peripheral blood mononuclear cells (PBMC) using fluorescence-activated cell sorting analysis as well as its effects on cytokine production using enzyme-linked immunosorbent assay. Whereas no inhibitor of spontaneous expression of adhesion molecules was reported, we found that PGE₁ inhibited spontaneous ICAM-1, B7.2, and CD40 expression on monocytes in a concentration-dependent manner but had no effect on the expression of B7.1 and CD40L. Although interleukin (IL)-18 induced the expression of ICAM-1, B7.2, CD40, and CD40L, PGE₁ prevented IL-18-induced expression of ICAM-1, B7.2, and CD40. We examined the involvement of five subtypes of PGE₁ receptors (IP, EP1, EP2, EP3, and EP4) in the effect of PGE₁ on the expression of these adhesion molecules using subtype-specific agonists. Among EP receptor agonists, EP2 and EP4 receptor agonists inhibited IL-18-elicited ICAM-1, B7.2, and CD40 expression. ONO-1301 (IP receptor agonist) prevented the expression of ICAM-1, B7.2, and CD40 regardless of the presence of IL-18 with the same potency as PGE₁. The effect of a combination of ONO-1301 and 11-deoxy (D)-PGE₁ (EP2/EP4 receptor agonist) on ICAM-1, B7.2, and CD40 expression mimicked that of PGE₁. Moreover, PGE₁ inhibited the production of IL-12 and interferon-γ in PBMC in the presence and absence of IL-18, whereas PGE₁ induced IL-10 production. In conclusion, IP receptor and EP2/EP4 receptor play an important role in the action of PGE₁ on the expression of adhesion molecules on monocytes and cytokine production.