Prostaglandin E2 downregulates interferon-gamma-induced intercellular adhesion molecule-1 expression via EP2 receptors in human gingival fibroblasts.
In the present study, the effect of prostaglandin E2 (PGE2) on intercellular adhesion molecule-1 (ICAM-1) expression in interferon-gamma (IFN-gamma)-stimulated human gingival fibroblasts (HGF) was investigated. Addition of PGE2 to HGF inhibited ICAM-1 expression elicited by IFN-gamma. As PGE2 elevated intercellular cyclic AMP (cAMP) levels in HGF in a dose-dependent fashion, the effect of dibutyryl cAMP and 8-bromo-cAMP, cAMP analogues, on IFN-gamma-elicited ICAM-1 expression was examined. Both the agents downregulated ICAM-1 expression in IFN-gamma-stimulated HGF. Next, we examined which subtype(s) of the four PGE2 receptor subtypes (EP1, EP2, EP3 and EP4) modulated the ICAM-1 expression elicited by IFN-gamma, using subtype-specific agonists or antagonists. An EP2/EP4 agonist, 11-deoxy-PGE1, attenuated IFN-gamma-elicited ICAM-1 expression in a concentration-dependent manner. A specific EP4 antagonist, AH-23848B, showed no effect on inhibition of IFN-gamma-elicited ICAM-1 expression by PGE2 and 11-deoxy-PGE1. Butaprost, an EP2-selective agonist, mimicked inhibition of IFN-gamma-elicited ICAM-1 expression by 11-deoxy-PGE1. An EP3 agonist, ONO-AP-324, was inert with respect to IFN-gamma-elicited ICAM-1 expression. Sulprostone, an EP1/EP3 agonist, showed stimulatory effect on ICAM-1 expression elicited by IFN-gamma. From these results, we suggest that PGE2 downregulates IFN-gamma-induced ICAM-1 expression in HGF, primarily via EP2 receptors by cAMP-dependent signaling pathways.
Noguchi
K
K
Department of Periodontology, Graduate School, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
Iwasaki
K
K
Shitashige
M
M
Murato
S
S
Ishikawa
I
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004336:Drug Antagonism; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D010120:Oxytocics / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000378:metabolism
D000970:Antineoplastic Agents; D010120:Oxytocics; D018078:Receptors, Prostaglandin E; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D015232:Dinoprostone