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More MS news articles for May 2004

Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis

Physiol Genomics. 2004 May 11
Spach KM, Pedersen LB, Nashold FE, Kayo T, Yandell BS, Prolla TA, Hayes CE.
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.

Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS) that develops in genetically-susceptible individuals who are exposed to undefined environmental risk factors.

Epidemiological, genetic, and biological evidence suggests that insufficient vitamin D may be an MS risk factor.

However, little is known about how vitamin D might be protective in MS.

We hypothesized that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) might regulate gene expression patterns in a manner that would resolve inflammation.

To test this hypothesis, experimental autoimmune encephalomyelitis (EAE) was induced in mice, 1,25-(OH)2D3 or a placebo was administered, and 6 h later, DNA microarray hybridization was performed with spinal cord RNA to analyze the gene expression patterns.

At this time, clinical, histopathological, and biological studies showed that the two groups did not difer in EAE disease, but changes in several 1,25-(OH)2D3-responsive genes indicated that the 1,25-(OH)2D3 had reached the CNS.

Compared to normal mice, placebo-treated mice with EAE showed increased expression of many immune system genes, confirming the acute inflammation.

When 1,25-(OH)2D3 was administered, several genes like glial fibrillary acidic protein and eukaryotic initiation factor 2 alpha kinase 4, whose expression increased or decreased with EAE, returned to homeostatic levels.

Also, two genes with pro-apoptotic functions, calpain-2 and caspase 8-associated protein, increased significantly.

A terminal deoxynucleotidyl transfer-mediated dUTP nicked end labeling study detected increased nuclear fragmentation in the 1,25-(OH)2D3-treated samples confirming increased apoptosis.

Together, these results suggest that sensitization of inflammatory cells to apoptotic signals may be one mechanism by which the 1,25-(OH)2D3 resolved EAE.