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

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-derive...

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Bibliographic Details
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
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Summary: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.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2006.07.009