Effect of sphingosine kinase modulators on interleukin-1β release, sphingosine 1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis

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• 作者：Mark Barbour ; Melissa McNaughton ; Stephanie D Boomkamp ; Neil MacRitchie ; Hui-Rong Jiang ; Nigel J Pyne and Susan Pyne
• 刊名：British Journal of Pharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：174
• 期：2
• 页码：210-222
• 全文大小：1478K
• ISSN：1476-5381

文摘

The sphingosine analogue, FTY720 (Gilenya^R), alleviates clinical disease progression in multiple sclerosis. Here, we variously assessed the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine kinase 2 substrate) on IL-1β formation, sphingosine 1-phosphate levels and expression of S1P₁ receptors. We also assessed the effect of compound 5 and ROMe in an experimental autoimmune encephalomyelitis (EAE) model in mice.