title: Aurintricarboxylic acid ameliorates experimental autoimmune encephalomyelitis by blocking chemokine-mediated pathogenic cell migration and infiltration.
abstract: Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Overactivation of CD4(+) T cells, especially the Th1 and Th17 subpopulations, is thought to be the direct cause of this disease. Aurintricarboxylic acid (ATA), an inhibitor of protein-nucleic acid interaction, has been reported to block with the JAK/STAT signaling pathway that is critical for Th cell differentiation. In this study, we discovered that ATA treatment significantly reduces the clinical score of EAE, but it does not directly inhibit the differentiation of Th1 and Th17 cells in vitro. ATA was found to block the chemotaxis and accumulation of dendritic cells in the spleen of EAE mice before the onset of the disease and to reduce the percentage of Th1 and Th17 cells in the spleen. Further study revealed that ATA also blocks the infiltration of pathogenic T cells into the CNS and blocks the onset of passive EAE. ATA was found to inhibit the functions of many chemokine receptors. By blocking chemokine-mediated migration of dendritic cells and pathogenic T cells, ATA alleviates the pathogenesis of EAE and might be used to treat autoimmune diseases, including multiple sclerosis.
authors.affiliation: CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Chai
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001312:Aurintricarboxylic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D038041:Lymphopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019707:Receptors, Chemokine; C445081:myelin oligodendrocyte glycoprotein (35-55); D001312:Aurintricarboxylic Acid