Abstract
Rolipram suppresses experimental autoimmune encephalomyelitis (EAE) and diminishes cell infiltration of the central nervous system (CNS). In Lewis rats with EAE, rolipram reduced matrix metalloproteinase-9 (MMP-9) gene expression in lymph node cells (LNCs) and spinal cord, decreased basal levels of nuclear (p50/p65) NF-kappaB in LNCs from treated rats, and impaired CD3 mediated NF-kappaB translocation. Rolipram reduced the luciferase activity directed by the NF-kappaB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-kappaB activity and the ability of a myelin basic protein (MBP) specific cell line to migrate across artificial basement membranes. IL-2 induced MMP-9 proteolytic activity was only slightly reduced indicating that additional factors contribute to inhibit cell migration mediated by rolipram.
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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Cell Movement / drug effects
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Cells, Cultured
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Interactions
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Electrophoretic Mobility Shift Assay / methods
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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 / metabolism*
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Gene Expression / drug effects*
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Luciferases / metabolism
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Lymph Nodes / cytology
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Lymphocytes / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Myelin Basic Protein / metabolism
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NF-kappa B / metabolism*
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Phosphodiesterase Inhibitors / administration & dosage*
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RNA, Messenger / biosynthesis
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Rats
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Rats, Inbred Lew
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Rolipram / administration & dosage*
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Spinal Cord / drug effects
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Spinal Cord / metabolism
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Transfection / methods
Substances
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Myelin Basic Protein
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NF-kappa B
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Phosphodiesterase Inhibitors
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RNA, Messenger
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Luciferases
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Matrix Metalloproteinase 9
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Rolipram