title: 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: Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA; Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, 250117, Shandong Province, China.
authors: Li
authors: L
authors: Xie
authors: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
authors: Jing
authors: J
authors: Chen
authors: Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA.
authors: Anthony
authors: A
authors: McMickle
authors: Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA.
authors: Nadia
authors: N
authors: Awar
authors: Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA.
authors: Soad
authors: S
authors: Nady
authors: C.A.I.R. Institute, The Mina and Everard Goodman, Faculty of Life Sciences, Bar Ilan University, Ramat Gan, 52900, Israel.
authors: Benjamin
authors: B
authors: Sredni
authors: Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Med. Sci., Little Rock, AR 72205, USA.
authors: Paul D
authors: PD
authors: Drew
authors: Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA. Electronic address: syu@astate.edu.
authors: Shiguang
authors: S
authors: Yu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005030:Ethylenes / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects
chemical_list: D016207:Cytokines; D005030:Ethylenes; D007155:Immunologic Factors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D005620:Freund's Adjuvant; D051058:Oncogene Protein v-akt
keywords: GM-CSF; IL-17; Inflammation; Signal transduction; Stat3; Th17 cells