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Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation.
Neurology 2011; 76(8 Suppl 3):S3-8Neur

Abstract

Sphingosine 1-phosphate (S1P) and 5 specific high-affinity S1P receptor (S1PR) subtypes, S1P(1-5), have important regulatory functions in normal physiology and disease processes, particularly involving the immune, central nervous, and cardiovascular systems. Within the immune system, downmodulation of S1P(1) prevents the egress of B and T cells from lymph nodes (LN) into the lymphatic circulation. This is especially relevant in certain autoimmune diseases, including multiple sclerosis (MS), in which demyelination and brain atrophy occur due to the presence of autoreactive lymphocytes within the CNS. Accordingly, S1P(1)-directed pharmacologic interventions that aim to retain these autoreactive lymphocytes in the LN and thus prevent their recirculation and subsequent infiltration into the CNS have been investigated as a means of preventing disease progression in patients with MS. Fingolimod (FTY720), a structural analog of sphingosine, is phosphorylated in vivo into fingolimod phosphate by sphingosine kinase-2. Fingolimod phosphate, which binds to S1PRs, has been shown to modulate the activity of S1P(1) in patients with MS and to reduce immune cell infiltration into the CNS, consistent with its previously established effects in animal models of the disease. Preclinical studies also suggest that fingolimod has beneficial effects within the CNS that are independent of its immune cell trafficking activity. This review highlights the normal physiologic processes modulated by S1P and S1PRs, and the therapeutic effects of S1PR modulation in the immune, central nervous, and cardiovascular systems.

Authors+Show Affiliations

Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Cornell University, New York, NY 10065, USA. tih2002@med.cornell.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

21339489

Citation

Hla, Timothy, and Volker Brinkmann. "Sphingosine 1-phosphate (S1P): Physiology and the Effects of S1P Receptor Modulation." Neurology, vol. 76, no. 8 Suppl 3, 2011, pp. S3-8.
Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology. 2011;76(8 Suppl 3):S3-8.
Hla, T., & Brinkmann, V. (2011). Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology, 76(8 Suppl 3), pp. S3-8. doi:10.1212/WNL.0b013e31820d5ec1.
Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the Effects of S1P Receptor Modulation. Neurology. 2011 Feb 22;76(8 Suppl 3):S3-8. PubMed PMID: 21339489.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. AU - Hla,Timothy, AU - Brinkmann,Volker, PY - 2011/2/23/entrez PY - 2011/2/26/pubmed PY - 2011/3/12/medline SP - S3 EP - 8 JF - Neurology JO - Neurology VL - 76 IS - 8 Suppl 3 N2 - Sphingosine 1-phosphate (S1P) and 5 specific high-affinity S1P receptor (S1PR) subtypes, S1P(1-5), have important regulatory functions in normal physiology and disease processes, particularly involving the immune, central nervous, and cardiovascular systems. Within the immune system, downmodulation of S1P(1) prevents the egress of B and T cells from lymph nodes (LN) into the lymphatic circulation. This is especially relevant in certain autoimmune diseases, including multiple sclerosis (MS), in which demyelination and brain atrophy occur due to the presence of autoreactive lymphocytes within the CNS. Accordingly, S1P(1)-directed pharmacologic interventions that aim to retain these autoreactive lymphocytes in the LN and thus prevent their recirculation and subsequent infiltration into the CNS have been investigated as a means of preventing disease progression in patients with MS. Fingolimod (FTY720), a structural analog of sphingosine, is phosphorylated in vivo into fingolimod phosphate by sphingosine kinase-2. Fingolimod phosphate, which binds to S1PRs, has been shown to modulate the activity of S1P(1) in patients with MS and to reduce immune cell infiltration into the CNS, consistent with its previously established effects in animal models of the disease. Preclinical studies also suggest that fingolimod has beneficial effects within the CNS that are independent of its immune cell trafficking activity. This review highlights the normal physiologic processes modulated by S1P and S1PRs, and the therapeutic effects of S1PR modulation in the immune, central nervous, and cardiovascular systems. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/21339489/Sphingosine_1_phosphate__S1P_:_Physiology_and_the_effects_of_S1P_receptor_modulation_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=21339489 DB - PRIME DP - Unbound Medicine ER -