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Sphingosine 1-phosphate receptor 1 (S1P(1)) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P(1) antagonist

Academic Article
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Overview

related to degree

  • Cahalan, Stuart Morgan, Ph.D. in Biology, Scripps Research 2004 - 2011

authors

  • Cahalan, Stuart Morgan
  • Gonzalez-Cabrera, P. J.
  • Nguyen, N.
  • Guerrero, M.
  • Cisar, E. A. G.
  • Leaf, N. B.
  • Brown, S. J.
  • Roberts, Edward
  • Rosen, Hugh

publication date

  • February 2013

journal

  • Molecular Pharmacology  Journal

abstract

  • Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1P(1) both cause lymphocyte sequestration in the lymph nodes. In the present study, we show that S1P(1) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P(1) agonists while upregulating S1P(1) on lymphocytes and endothelial cells. Additionally, we show that S1P(1) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P(1) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P(1) antagonism is sufficient to alleviate autoimmune pathology.

subject areas

  • Animals
  • CHO Cells
  • Cell Line
  • Central Nervous System
  • Cricetinae
  • Encephalomyelitis, Autoimmune, Experimental
  • Endothelial Cells
  • Female
  • HEK293 Cells
  • Humans
  • Immunosuppressive Agents
  • Lymph Nodes
  • Lymphocytes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Lysosphingolipid
  • Up-Regulation
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Identity

PubMed Central ID

  • PMC3558813

International Standard Serial Number (ISSN)

  • 0026-895X

Digital Object Identifier (DOI)

  • 10.1124/mol.112.082958

PubMed ID

  • 23204443
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Additional Document Info

start page

  • 316

end page

  • 321

volume

  • 83

issue

  • 2

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