Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice.
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.
Webb
Michael
M
Molecular Neuroscience Laboratory, Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA. xhua@san.rr.com
Tham
Chui-Se
CS
Lin
Fen-Fen
FF
Lariosa-Willingham
Karen
K
Yu
Naichen
N
Hale
Jeffrey
J
Mandala
Suzanne
S
Chun
Jerold
J
Rao
Tadimeti S
TS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D000068876:Fingolimod Hydrochloride; D005786:Gene Expression Regulation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008231:Lymphopenia / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D008815:Mice, Inbred Strains; D008942:Mitoxantrone / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D018991:Myelin Proteolipid Protein; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D049312:Receptors, Lysophospholipid; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013110:Sphingosine / Q000031:analogs & derivatives; D013997:Time Factors
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011409:Propylene Glycols; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine