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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Astrocytes / drug effects*
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Astrocytes / metabolism
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Benzoates / pharmacology
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Benzylamines / pharmacology
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Blotting, Western / methods
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Cells, Cultured
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Cholesterol / metabolism
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Cholesterol / pharmacology*
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DNA-Binding Proteins / physiology*
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Desmosterol / analogs & derivatives
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Desmosterol / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation / drug effects*
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Hydrocarbons, Fluorinated
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Interferon Regulatory Factor-1 / metabolism
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Interferon-beta / metabolism
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Ketocholesterols / pharmacology
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Lipopolysaccharides / pharmacology*
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Liver X Receptors
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Models, Biological
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Nitric Oxide Synthase Type II / metabolism*
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Orphan Nuclear Receptors
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RNA, Messenger / metabolism
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Rats
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Receptors, Cytoplasmic and Nuclear / physiology*
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Sulfonamides / pharmacology
Substances
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Benzoates
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Benzylamines
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DNA-Binding Proteins
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Enzyme Inhibitors
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GW 3965
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Hydrocarbons, Fluorinated
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Interferon Regulatory Factor-1
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Ketocholesterols
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Lipopolysaccharides
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Liver X Receptors
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Orphan Nuclear Receptors
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Sulfonamides
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T0901317
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Desmosterol
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22(R)-hydroxydesmosterol
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Interferon-beta
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Cholesterol
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Nitric Oxide Synthase Type II
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7-ketocholesterol