Abstract
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.
Keywords:
GM-CSF; IL-17; Inflammation; Signal transduction; Stat3; Th17 cells.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism
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Cell Polarity / drug effects
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Cell Proliferation / drug effects
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Cytokines / biosynthesis
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Cytokines / immunology
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Cytokines / metabolism*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Ethylenes / pharmacology*
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Ethylenes / therapeutic use*
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Female
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Freund's Adjuvant / pharmacology
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use
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Mice
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Mice, Inbred C57BL
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Myelin-Oligodendrocyte Glycoprotein / pharmacology
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Oncogene Protein v-akt / metabolism
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Peptide Fragments / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Spinal Cord / pathology
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Th17 Cells / drug effects
Substances
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Cytokines
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Ethylenes
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Immunologic Factors
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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myelin oligodendrocyte glycoprotein (35-55)
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ammonium trichloro(dioxoethylene-O,O'-)tellurate
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Freund's Adjuvant
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Oncogene Protein v-akt