The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Aug 15;273(1-2):31-41. doi: 10.1016/j.jneuroim.2014.05.015. Epub 2014 Jun 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Polarity / drug effects
  • Cell Proliferation / drug effects
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Ethylenes / pharmacology*
  • Ethylenes / therapeutic use*
  • Female
  • Freund's Adjuvant / pharmacology
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / pharmacology
  • Oncogene Protein v-akt / metabolism
  • Peptide Fragments / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Spinal Cord / pathology
  • Th17 Cells / drug effects

Substances

  • Cytokines
  • Ethylenes
  • Immunologic Factors
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • ammonium trichloro(dioxoethylene-O,O'-)tellurate
  • Freund's Adjuvant
  • Oncogene Protein v-akt