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Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice

Academic Article
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Overview

authors

  • Webb, M.
  • Tharn, C. S.
  • Lin, F. F.
  • Lariosa-Willingham, K.
  • Yu, N. C.
  • Hale, J.
  • Mandala, S.
  • Chun, Jerold
  • Rao, T. S.

publication date

  • August 2004

journal

  • Journal of Neuroimmunology  Journal

abstract

  • FTY720 is a prodrug for FTY-phosphate, an agonist at four of the five known receptors for sphingosine-1-phosphate (S1P). We show that administration of either FTY720 or FTY-P to SJL mice with established relapsing-remitting experimental autoimmune encephalitis (EAE) results in a rapid and sustained improvement in their clinical status, and a reversal of changes in expression of mRNAs encoding some myelin proteins and inflammatory mediators. EAE produced by adoptively transferring lymph node cells from immunized mice to na?ve hosts is similarly ameliorated by FTY-P. Treatment with FTY-P is accompanied by a dose-responsive peripheral lymphopoenia.
  • FTY720 is a prodrug for FTY-phosphate, an agonist at four of the five known receptors for sphingosine-1-phosphate (S1P). We show that administration of either FTY720 or FTY-P to SJL mice with established relapsing-remitting experimental autoimmune encephalitis (EAE) results in a rapid and sustained improvement in their clinical status, and a reversal of changes in expression of mRNAs encoding some myelin proteins and inflammatory mediators. EAE produced by adoptively transferring lymph node cells from immunized mice to naïve hosts is similarly ameliorated by FTY-P. Treatment with FTY-P is accompanied by a dose-responsive peripheral lymphopoenia.

subject areas

  • Animals
  • Antineoplastic Agents
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Encephalomyelitis, Autoimmune, Experimental
  • Female
  • Fingolimod Hydrochloride
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Immunosuppressive Agents
  • Interferon-gamma
  • Lymphocytes
  • Lymphopenia
  • Mice
  • Mice, Inbred Strains
  • Mitoxantrone
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Peptide Fragments
  • Propylene Glycols
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sphingosine
  • Time Factors
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Research

keywords

  • FTY720
  • gene expression
  • lymphopoenia
  • relapsing-remitting EAE
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Identity

International Standard Serial Number (ISSN)

  • 0165-5728

Digital Object Identifier (DOI)

  • 10.1016/j.jneuroim.2004.04.015

PubMed ID

  • 15265669
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Additional Document Info

start page

  • 108

end page

  • 121

volume

  • 153

issue

  • 1-2

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