CHARACTERIZATION OF THE LPS-STIMULATED EXPRESSION OF EP2 AND EP4 PROSTAGLANDIN-E RECEPTORS IN MOUSE MACROPHAGE-LIKE CELL-LINE, J774.1

The expression of prostaglandin (PG) E receptor subtypes were characte rized in J774.1, a mouse macrophage-like cell Line. EP2- and EP4-mRNAs were found to be expressed. The expression of EP2 mRNA increased by t he addition of lipopolysaccharide (LPS) in a dose-dependent manner. EP 2 mRNA rapidly increased by more than 5-fold of the control level at 1 h, and decreased after 4 h. EP4 mRNA increased by only 2-fold of the control at 2 h. Gamma interferon inhibited both basal and LPS-induced expression of EP2 mRNA but did not affect the expression level of EP4 mRNA. When tumor necrosis factor-alpha (TNF-alpha) accumulation was me asured after the treatment of the cells with LPS for 90 min, PGE(2) wa s found to inhibit this accumulation, but butaprost, an EP2-selective agonist, did not. When TNF-alpha release was measured after the treatm ent of the cells with LPS for 8 h, accumulation was inhibited by butap rost as well as PGE(2). These results indicated that the inhibitory ef fects of PGE(2) on TNF-alpha production are mediated by EP2 and EP4 in macrophages, and that expression regulation of EP2 and EP4 in macroph ages is quite different. (C) 1998 Academic Press.