sq-23377 and myelin-oligodendrocyte-glycoprotein-(35-55)

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.. 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.. Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Artemisinins; Artesunate; Brefeldin A; Cell Movement; Central Nervous System; Cytokines; Disease Models, Animal; DNA-Binding Proteins; Encephalomyelitis, Autoimmune, Experimental; Enzyme Inhibitors; Female; Flow Cytometry; Gene Expression Regulation; Ionomycin; Leukocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Phorbol Esters

Oxidized phospholipids (Ox-PLs) are generated in abundance at sites of inflammation. Recent studies have indicated that Ox-PLs may also exhibit anti-inflammatory activities. In this study, we investigated the beneficial effect of VB-201, a pure synthetic Ox-PL analog that we synthesized, on the development of a central nervous system (CNS) autoimmune inflammatory disease, in vivo. Oral administration of VB-201 ameliorated the severity of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide MOG35-55, and restrained the encephalogenicity of MOG35-55-specific T-cells. Our data presents a novel prospect for the role of Ox-PL analogs in CNS inflammatory diseases.

Topics: Animals; Bone Marrow Cells; Bromodeoxyuridine; CD4 Antigens; Cell Differentiation; Central Nervous System; Cytokines; Dendritic Cells; Disease Models, Animal; Drug Interactions; Encephalitis; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Female; Forkhead Transcription Factors; Freund's Adjuvant; Glycerylphosphorylcholine; Glycoproteins; Ionomycin; Ionophores; Lymph Nodes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Pertussis Toxin; Phosphorylcholine; Polymethacrylic Acids; Severity of Illness Index; T-Lymphocytes; Time Factors