Liver X receptor ligands inhibit the lipopolysaccharide-induced expression of microsomal prostaglandin E synthase-1 and diminish prostaglandin E2 production in murine peritoneal macrophages. 2007

Yuichi Ninomiya, and Toshimichi Yasuda, and Masashi Kawamoto, and Osafumi Yuge, and Yasushi Okazaki
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

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.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D010537 Peritoneum A membrane of squamous EPITHELIAL CELLS, the mesothelial cells, covered by apical MICROVILLI that allow rapid absorption of fluid and particles in the PERITONEAL CAVITY. The peritoneum is divided into parietal and visceral components. The parietal peritoneum covers the inside of the ABDOMINAL WALL. The visceral peritoneum covers the intraperitoneal organs. The double-layered peritoneum forms the MESENTERY that suspends these organs from the abdominal wall. Parietal Peritoneum,Peritoneum, Parietal,Peritoneum, Visceral,Visceral Peritoneum,Parametrium,Parametriums
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000071518 Liver X Receptors Nuclear receptors that bind OXYSTEROLS and function as heterodimers with RETINOID X RECEPTORS. They have important functions in regulating cholesterol homeostasis, ENERGY METABOLISM; INFLAMMATION; and the immune response. LXR-Alpha Protein,LXRalpha Protein,LXRbeta Protein,Liver X Receptor,Liver X Receptor Alpha,Liver X Receptor Beta,Liver X Receptor-Alpha,Liver X Receptor-Beta,NR1H2 Protein,NR1H3 Protein,Nuclear Orphan Receptor LXR-Alpha,Nuclear Oxysterol Receptors,Nuclear Receptor Subfamily 1, Group H, Member 2,Nuclear Receptor Subfamily 1, Group H, Member 3,Oxysterols Receptor LXR-Alpha,Oxysterols Receptor LXR-Beta,LXR Alpha Protein,LXR-Alpha, Oxysterols Receptor,LXR-Beta, Oxysterols Receptor,Nuclear Orphan Receptor LXR Alpha,Oxysterol Receptors, Nuclear,Oxysterols Receptor LXR Alpha,Oxysterols Receptor LXR Beta
D000071876 Prostaglandin-E Synthases Oxidoreductases that catalyze the GLUTATHIONE-dependent oxidoreduction of PROSTAGLANDIN H2 to PROSTAGLANDIN E2. Cytosolic Prostaglandin E2 Synthase,Endoperoxide Isomerase,PGE2 Isomerase,PGE2 Synthase,PGR2 E-Isomerase,PTGES2 Protein,PTGES3 Protein,Prostaglandin E Isomerase,Prostaglandin E Synthase,Prostaglandin E Synthase 1,Prostaglandin E Synthase 2,Prostaglandin E Synthase 3,Prostaglandin E Synthase-1,Prostaglandin E Synthases,Prostaglandin E2 Synthase,Prostaglandin Endoperoxide E Isomerase,Prostaglandin H2 E-Isomerase,Prostaglandin H2-Prostaglandin E2 Isomerase,Prostaglandin R2 E-Isomerase,Prostaglandin-E Synthase,E Synthases, Prostaglandin,Isomerase, Endoperoxide,Isomerase, PGE2,Isomerase, Prostaglandin E,PGR2 E Isomerase,Prostaglandin H2 E Isomerase,Prostaglandin H2 Prostaglandin E2 Isomerase,Prostaglandin R2 E Isomerase,Synthase, PGE2,Synthase, Prostaglandin E,Synthase, Prostaglandin E2,Synthase, Prostaglandin-E,Synthases, Prostaglandin E,Synthases, Prostaglandin-E

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