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

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.

• Authors: Li Xie, Jing Chen, Anthony McMickle, Nadia Awar, Soad Nady, Benjamin Sredni, Paul D Drew, Shiguang Yu
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 273 Issue 1-2 Pg. 31-41 (Aug 15 2014) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 24975323 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• 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

Topics

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