RT Journal Article
SR Electronic
T1 Unique Regulation Profile of Prostaglandin E<sub>1</sub> on Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1188
OP 1195
DO 10.1124/jpet.103.056432
VO 307
IS 3
A1 Hideo Kohka Takahashi
A1 Hiromi Iwagaki
A1 Ryuji Tamura
A1 Dong Xue
A1 Masahiro Sano
A1 Shuji Mori
A1 Tadashi Yoshino
A1 Noriaki Tanaka
A1 Masahiro Nishibori
YR 2003
UL http://jpet.aspetjournals.org/content/307/3/1188.abstract
AB 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-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. The American Society for Pharmacology and Experimental Therapeutics