Liver X receptor ligands inhibit the lipopolysaccharide-induced expression of microsomal prostaglandin E synthase-1 and diminish prostaglandin E2 production in murine peritoneal macrophages

• Published in: The Journal of steroid biochemistry and molecular biology 2007, Vol.103 (1), p.44-50
• Main Authors: NINOMIYA, Yuichi, YASUDA, Toshimichi, KAWAMOTO, Masashi, YUGE, Osafumi, OKAZAKI, Yasushi
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dinoprostone - metabolism; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Intramolecular Oxidoreductases - metabolism; Ligands; Lipopolysaccharides - pharmacology; Liver X Receptors; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Microsomes - enzymology; Microsomes - metabolism; Orphan Nuclear Receptors; Peritoneum - cytology; Peritoneum - metabolism; Prostaglandin-E Synthases; Prostaglandins. Arachidonic acid metabolites; Receptors, Cytoplasmic and Nuclear - metabolism; Vertebrates: endocrinology
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2006.07.009

Microsomal prostaglandin E synthase (mPGES)-1, which is dramatically induced in macrophages by inflammatory stimuli such as lipopolysaccharide (LPS), catalyzes the conversion of cyclooxygenase-2 (COX-2) reaction product prostaglandin H(2) (PGH(2)) into prostaglandin E(2) (PGE(2)). The mPGES-1-derived PGE(2) is thought to help regulate inflammatory responses. On the other hand, excess PGE(2) derived from mPGES-1 contributes to the development of inflammatory diseases such as arthritis and inflammatory pain. Here, we examined the effects of liver X receptor (LXR) ligands on LPS-induced mPGES-1 expression in murine peritoneal macrophages. The LXR ligands 22(R)-hydroxycholesterol (22R-HC) and T0901317 reduced LPS-induced expression of mPGES-1 mRNA and mPGES-1 protein as well as that of COX-2 protein. However, LXR ligands did not influence the expression of microsomal PGES-2 (mPGES-2) or cytosolic PGES (cPGES) protein. Consequently, LXR ligands suppressed the production of PGE(2) in macrophages. These results suggest that LXR ligands diminish PGE(2) production by inhibiting the LPS-induced gene expression of the COX-2-mPGES-1 axis in LPS-activated macrophages.