Abstract
Clinical symptoms in MOG-induced EAE mice significantly exacerbated following chondroitin sulfate A (CS-A) injection, whereas administration of a degraded product, CSPG-DS, caused dramatic inhibition of EAE development. Also, administration of CSPG-DS but not CS-A, after the onset of clinical symptoms of EAE, was able to suppress the disease. Further studies demonstrated that CS-A up-regulated STAT4 expression and thus, induced IFN-gamma production and Th1 CD4 T cell differentiation. CS-A also up-regulated STAT3 and IL-23 expression and thus increased IL-17 producing T cells. CSPG-DS treatment both in vivo and in vitro decreased TNFalpha production from splenocytes. In vitro and in vivo studies indicated that CSPG-DS treatment in EAE mice significantly blocked migration of lymphocytes, whereas CS-A treatment increased lymphocyte infiltration in the brain.
Copyright 2010. Published by Elsevier B.V.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / physiology
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Amino Acid Sequence
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
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Anti-Inflammatory Agents, Non-Steroidal / metabolism
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Chondroitin Sulfate Proteoglycans / administration & dosage*
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Chondroitin Sulfate Proteoglycans / metabolism
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Chondroitin Sulfate Proteoglycans / physiology
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Disaccharides / administration & dosage*
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Disaccharides / metabolism
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Disaccharides / physiology
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Disease Models, Animal*
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / toxicity
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / immunology*
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Multiple Sclerosis / pathology
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / toxicity
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Toxoids / antagonists & inhibitors
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Toxoids / toxicity
Substances
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Adjuvants, Immunologic
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Anti-Inflammatory Agents, Non-Steroidal
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Chondroitin Sulfate Proteoglycans
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Disaccharides
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Glycoproteins
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Toxoids
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myelin oligodendrocyte glycoprotein (35-55)
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pertussis toxoid