Abstract
Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and fingolimod treatments would have synergistic effects in EAE. We show that combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-β levels in EAE mice. Combination therapy also modulated IL-17 and TGF-β concentration, RoRγt and Foxp3 mRNA levels, and Th17 cell and Treg frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE mice. Our findings provide insight into using this drug combination to treat EAE.
Keywords:
Experimental autoimmune encephalomyelitis; Fingolimod; Multiple sclerosis; Rapamycin; Th17; Treg.
Copyright © 2018 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Drug Therapy, Combination
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Female
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Fingolimod Hydrochloride / administration & dosage*
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Immunosuppressive Agents / administration & dosage
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MAP Kinase Signaling System / drug effects*
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MAP Kinase Signaling System / physiology
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Mice
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Mice, Inbred C57BL
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Sirolimus / administration & dosage*
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T-Lymphocytes, Regulatory / drug effects*
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T-Lymphocytes, Regulatory / physiology
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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TOR Serine-Threonine Kinases / metabolism
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Th17 Cells / drug effects*
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Th17 Cells / physiology
Substances
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Immunosuppressive Agents
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mTOR protein, mouse
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Fingolimod Hydrochloride
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Sirolimus