ammonium-trichloro(dioxoethylene-o-o--)tellurate and myelin-oligodendrocyte-glycoprotein-(35-55)

We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and RORγt, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Finally, by real-time PCR analysis we showed that AS101 reduces the IL-17, IFN-γ, GM-CSF, and IL-6 mRNA expression in inflammatory cells of spinal cords. Additionally, flow cytometry analysis also indicated that the CD4+ T cells and IL-17 and GM-CSF-producing cells were reduced in the spinal cords of AS101 treated mice compared to those treated with PBS.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Polarity; Cell Proliferation; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Encephalomyelitis, Autoimmune, Experimental; Ethylenes; Female; Freund's Adjuvant; Immunologic Factors; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Oncogene Protein v-akt; Peptide Fragments; Signal Transduction; Spinal Cord; Th17 Cells