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 characterized 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 the addition of lipopolysaccharide (LPS) in a dose-dependent manner. EP2 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 measured after the treatment ofthe cells with LPS for 90 min, PGE2 was found to inhibit this accumulation, but butaprost, an EP2-selective agonist, did not. When TNF-alpha release was measured after the treatment of the cells with LPS for 8 h, accumulation was inhibited by butaprost as well as PGE2. These results indicated that the inhibitory effects of PGE2 on TNF-alpha production are mediated by EP2 and EP4 in macrophages, and that expression regulation of EP2 and EP4 in macrophages is quite different.
Katsuyama
M
M
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Ikegami
R
R
Karahashi
H
H
Amano
F
F
Sugimoto
Y
Y
Ichikawa
A
A
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D011459:Prostaglandins E, Synthetic; C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone