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

Li Xie; Jing Chen; Anthony McMickle; Nadia Awar; Soad Nady; Benjamin Sredni; Paul D. Drew; Shiguang Yu

doi:10.1016/j.jneuroim.2014.05.015

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

Li Xie, Jing Chen, Anthony McMickle, Nadia Awar, Soad Nady, Benjamin Sredni, Paul D. Drew, Shiguang Yu

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14 Scopus citations

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.

Original language	English
Pages (from-to)	31-41
Number of pages	11
Journal	Journal of Neuroimmunology
Volume	273
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2014.05.015
State	Published - 15 Aug 2014

Bibliographical note

Funding Information:
This study was supported by Arkansas Biosciences Institute (ABI) Fund , Arkansas State University Faculty Fund , NIH grant number p20GM103429 from the IDeA Networks of Biomedical Research Excellence (INBRE) Program of the National Center for Research Resources, and NSF MRI . N. Awar was an ABI Summer Biotechnology Internship Recipient .

Funding

This study was supported by Arkansas Biosciences Institute (ABI) Fund , Arkansas State University Faculty Fund , NIH grant number p20GM103429 from the IDeA Networks of Biomedical Research Excellence (INBRE) Program of the National Center for Research Resources, and NSF MRI . N. Awar was an ABI Summer Biotechnology Internship Recipient .

Funders	Funder number
Arkansas State University Faculty Fund
INBRE
NSF MRI
Networks of Biomedical Research Excellence
National Institutes of Health
National Institute of General Medical Sciences	P20GM103429
National Center for Research Resources
Arkansas Biosciences Institute

Keywords

GM-CSF
IL-17
Inflammation
Signal transduction
Stat3
Th17 cells

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10.1016/j.jneuroim.2014.05.015

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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.",

keywords = "GM-CSF, IL-17, Inflammation, Signal transduction, Stat3, Th17 cells",

author = "Li Xie and Jing Chen and Anthony McMickle and Nadia Awar and Soad Nady and Benjamin Sredni and Drew, {Paul D.} and Shiguang Yu",

note = "Funding Information: This study was supported by Arkansas Biosciences Institute (ABI) Fund , Arkansas State University Faculty Fund , NIH grant number p20GM103429 from the IDeA Networks of Biomedical Research Excellence (INBRE) Program of the National Center for Research Resources, and NSF MRI . N. Awar was an ABI Summer Biotechnology Internship Recipient .",

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AU - Xie, Li

AU - Chen, Jing

AU - McMickle, Anthony

AU - Awar, Nadia

AU - Nady, Soad

AU - Sredni, Benjamin

AU - Drew, Paul D.

AU - Yu, Shiguang

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AB - 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.

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

Abstract

Bibliographical note

Funding

Keywords

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