Mediation of the SPHK1/S1P Pathway Following Vitamin D Treatment of MS/EAE

Abstract Sphingosine-1-phosphate (S1P) is a bioactive lipid that distributed in a wide variety of body tissues, especially inflammatory tissues. We observed that S1P plays an important role in the pathogenesis of Experimental allergic encephalomyelitis (EAE), the animal model of Multiple sclerosis (MS). Additionally, Vitamin D is observed to be a key determinant in the regulation of S1P. We monitored the effects of Vitamin D on Sphingosine kinase type 1 (SPHK1), an important synthetase associated with S1P. The associated results suggest a reduction in SPHK1 in the spinal cords of EAE rats whose diets supplement with Vitamin D. Many of the biological functions that are traditionally associated with Vitamin D is mediated through the Vitamin D receptor (VDR). Indeed, these interactions play a major role in the regulation of transcription of many target genes. As part of this analysis, we revealed the relationship between VDR and SPHK1. This is performed using over-expression experiments and observations relating to the interference effects of VDR on SPHK1. Our results verify that expression of the factor S1P, which is associated with EAE, is caused by alterations in SPHK1 levels. This relationship is regulated by VDR. Consequently, immune regulatory mechanisms associate with Vitamin D adjuvant therapy, used for the treatment of MS, may be involved in the regulation of SPHK1. This regulatory role may ultimately modulate the levels of S1P in cells. This report focuses on the relationship between SPHK-S1P and Vitamin D and provides a potentially novel approach for the treatment of MS.