title: Liver X receptor ligands inhibit the lipopolysaccharide-induced expression of microsomal prostaglandin E synthase-1 and diminish prostaglandin E2 production in murine peritoneal macrophages.
abstract: 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.
authors.affiliation: Department of Immunology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. ninomiya@saitama-med.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Osafumi
authors.initials: O
authors.lastname: Yuge
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000201:enzymology* / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; C000605866:Ptges2 protein, mouse; D015232:Dinoprostone