S1P1 receptor subtype inhibits demyelination and regulates chemokine release in cerebellar slice cultures

Sheridan, Graham K.; Dev, Kumlesh K.

Abstract

Sphingosine-1-phosphate receptors (S1PRs) are drug targets for the compound FTY720, which is the first oral therapy developed for treatment of relapsing-remitting multiple sclerosis. S1PRs play a variety of functional roles in the differentiation, proliferation, survival and/or migration of neurons and glia. In this study, rat organotypic cerebellar slice cultures were used to assess whether S1PRs play a role in demyelination induced by lysolecithin (LPC). The data demonstrated that FTY720 and SEW2871 (a S1P1R-specific agonist) inhibited LPC-induced demyelination as assessed by myelin basic protein (MBP) immunofluorescence. Treatment with both drugs for 48 h also induced an increase in S1P1R expression in astrocytes. Moreover, FTY720 and SEW2871 inhibited the release of several chemokines in conditions of LPC-induced demyelination, including LIX (CXCL5), MIP-1alpha, and MIP-3alpha. Taken together, the data suggest that activation of S1P1Rs prevents LPC-induced demyelination via a mechanism involving a reduction of chemotactic chemokine release. The study supports the concept that FTY720 attenuates demyelination by not only preventing S1PR-mediated T cell migration into the CNS but also by limiting cytokine communication between cells of the immune system and the CNS. © 2011 Wiley Periodicals, Inc.

Citation

Sheridan, G. K., & Dev, K. K. (2012). S1P1 receptor subtype inhibits demyelination and regulates chemokine release in cerebellar slice cultures. Glia, 60(3), 382-392. https://doi.org/10.1002/glia.22272

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2011
• Online Publication Date: Nov 22, 2011
• Publication Date: 2012-03
• Deposit Date: Aug 16, 2022
• Journal: GLIA
• Print ISSN: 0894-1491
• Electronic ISSN: 1098-1136
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 60
• Issue: 3
• Pages: 382-392
• DOI: https://doi.org/10.1002/glia.22272
• Public URL: https://nottingham-repository.worktribe.com/output/10076734
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/glia.22272