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INFLAMMATION AND IMMUNOPHARMACOLOGY

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

Departments of Pharmacology (H.K.T., S.M., M.N.), Tumour Biology (H.K.T., H.I., R.T., D.X., N.T.), and Pathology (M.S., T.Y.), Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

In the present study, we examined the effects of prostaglandin E₁ (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- 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.

Address correspondence to: Dr. Masahiro Nishibori, Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: mbori{at}md.okayamau.ac.jp

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