Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis.
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.
Zhou
Juhua
J
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
Nagarkatti
Prakash
P
Zhong
Yin
Y
Nagarkatti
Mitzi
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D004187:Disaccharides / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D014121:Toxoids / Q000037:antagonists & inhibitors / Q000633:toxicity
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011508:Chondroitin Sulfate Proteoglycans; D004187:Disaccharides; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014121:Toxoids; C445081:myelin oligodendrocyte glycoprotein (35-55); C051093:pertussis toxoid