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Oxysterols suppress inducible nitric oxide synthase expression in lipopolysaccharide-stimulated astrocytes through liver X receptor.

Authors
Lee, CS; Joe, EH; Jou, I
Citation
Neuroreport, 17(2):183-187, 2006
Journal Title
Neuroreport
ISSN
0959-49651473-558X
Abstract
Cholesterols are enriched in the brain and can be oxidized to oxysterols by several processes. Oxysterols are transport forms of cholesterols across cell membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols in brain inflammation, we treated lipopolysaccharide-stimulated rat brain astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol. Both oxysterols suppressed inducible nitric oxide synthase expression and nitric oxide release as well as upstream signaling molecules including interferon-beta, phosphorylated signal transducer and activator of transcription 1/3, and interferon regulatory factor-1. Oxysterols are known as liver X receptor agonists, and inhibitory effects were also observed with synthetic agonists of liver X receptor and retinoid X receptor. Thus, we conclude that it is most likely mediated by liver X receptor/retinoid X receptor heterodimers.
MeSH terms
AnimalsAnimals, NewbornAstrocytes/drug effects*Astrocytes/metabolismBenzoic Acids/pharmacologyBenzylamines/pharmacologyBlotting, Western/methodsCells, CulturedCholesterol/metabolismCholesterol/pharmacology*DNA-Binding Proteins/physiology*Desmosterol/analogs & derivativesDesmosterol/pharmacologyDose-Response Relationship, DrugDrug InteractionsEnzyme Activation/drug effectsEnzyme Inhibitors/pharmacologyGene Expression Regulation/drug effects*Hydrocarbons, FluorinatedInterferon Regulatory Factor-1/metabolismInterferon-beta/metabolismKetocholesterols/pharmacologyLipopolysaccharides/pharmacology*Models, BiologicalNitric Oxide Synthase Type II/metabolism*Orphan Nuclear ReceptorsRNA, Messenger/metabolismRatsReceptors, Cytoplasmic and Nuclear/physiology*Reverse Transcriptase Polymerase Chain Reaction/methodsSulfonamides/pharmacology
PMID
16407768
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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