Abstract
Urate (UA) selectively scavenges peroxynitrite-dependent radicals and suppresses CNS inflammation through effects that are manifested at the blood-brain barrier (BBB). ICAM-1 upregulation in the spinal cord tissues of myelin basic protein (MBP) immunized mice is selectively inhibited by UA treatment. In contrast, the expression of ICAM-1 and other adhesion molecules by circulating cells is unchanged. Moreover, TNF-alpha expression in the CNS tissues of MBP-immunized mice is suppressed by UA treatment but TNF-alpha-induced ICAM-1 expression on neurovascular endothelial cells is not. Therefore the effect of UA on ICAM-1 upregulation in the CNS tissues is likely due to its known contribution to the maintenance of BBB integrity in MBP-immunized mice which in turn inhibits cell invasion into the CNS and prevents TNF-alpha production in CNS tissues.
Copyright 2004 Elsevier B.V.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blood-Brain Barrier / drug effects*
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Blood-Brain Barrier / immunology
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / immunology
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Disease Models, Animal
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / immunology
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Endothelium, Vascular / metabolism
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Female
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Free Radical Scavengers / pharmacology
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Free Radical Scavengers / therapeutic use
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Free Radicals / immunology
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Free Radicals / metabolism
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Intercellular Adhesion Molecule-1 / drug effects
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Intercellular Adhesion Molecule-1 / immunology
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Intercellular Adhesion Molecule-1 / metabolism*
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Mice
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Myelin Basic Protein / immunology
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Neurons / drug effects
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Neurons / immunology
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Neurons / metabolism
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Nitric Oxide Synthase / drug effects
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Nitric Oxide Synthase / immunology
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Peroxynitrous Acid / metabolism
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Spinal Cord / drug effects*
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Spinal Cord / metabolism
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Spinal Cord / physiopathology
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Tumor Necrosis Factor-alpha / drug effects
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / immunology
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Uric Acid / pharmacology*
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Uric Acid / therapeutic use
Substances
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Free Radical Scavengers
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Free Radicals
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Myelin Basic Protein
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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Peroxynitrous Acid
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Uric Acid
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse