1. Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System
- Author
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Thais Fernanda de Campos Fraga-Silva, Ana Carolina de Carvalho, Alexandre Leite Rodrigues de Oliveira, Rodolfo Thomé, Thiago Alves da Costa, Liana Verinaud, Larissa Lumi Watanabe Ishikawa, and Alexandrina Sartori
- Subjects
0301 basic medicine ,Central Nervous System ,Leukocyte migration ,Anti-Inflammatory Agents ,Artesunate ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Movement ,Phorbol Esters ,Leukocytes ,Pharmacology (medical) ,Enzyme Inhibitors ,Mice, Knockout ,biology ,Ionomycin ,Experimental autoimmune encephalomyelitis ,Flow Cytometry ,Artemisinins ,DNA-Binding Proteins ,Psychiatry and Mental health ,Cytokines ,Female ,Encephalomyelitis, Autoimmune, Experimental ,Myelin oligodendrocyte glycoprotein ,03 medical and health sciences ,Immune system ,Physiology (medical) ,medicine ,Animals ,Neuroinflammation ,Pharmacology ,Autoimmune disease ,Analysis of Variance ,Brefeldin A ,business.industry ,Multiple sclerosis ,Original Articles ,medicine.disease ,Peptide Fragments ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,Immunology ,biology.protein ,Myelin-Oligodendrocyte Glycoprotein ,business ,030215 immunology - Abstract
SummaryBackground and Aims Experimental autoimmune encephalomyelitis (EAE) is T-cell-dependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics. Artesunate (Art) is a semi-synthetic sesquiterpene derivative from artemisinin and has been shown to reduce the clinical signs of autoimmune disease models through mechanisms not yet understood. In this study, we aimed to evaluate whether administration of Art would ameliorate EAE. Methods and Results C57BL6 mice were immunized with MOG35–55 peptide to induce EAE. At the same time, Art treatment started (3 mg/kg/day via i.p.) for five consecutive days. We found that Art treatment reduced the clinical signs of EAE and that correlated with a reduced infiltration of cells in the CNS. Disease amelioration did not correlate with immunomodulation as recall responses, leukocyte subpopulations, and gene expression analysis were similar among treated and untreated mice. Ultimately, further analysis provided data indicating that a possible mechanism of action for Art is dependent on the cellular migration to the CNS. Conclusions Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS.
- Published
- 2016