Hypomethylating Agent 5‐Aza‐2′‐deoxycytidine (DAC) Ameliorates Multiple Sclerosis in Mouse Models. Issue 12 (December 2014)

• Record Type: Journal Article
• Authors: Mangano, Katia; Fagone, Paolo; Bendtzen, Klaus; Meroni, Pier Luigi; Quattrocchi, Cinzia; Mammana, Santa; Di Rosa, Michelino; Malaguarnera, Lucia; Coco, Marinella; Magro, Gaetano; Di Marco, Roberto; Nicoletti, Ferdinando
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 12(2014:Dec.)
• Page Start: 1918
• Page End: 1925
• Publication Date: 2014-12
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24641
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcp24641-sec-0001" sec-type="section"> <p>Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5‐aza‐2′‐deoxycytidine (DAC) in two murine models of experimental allergic encephalomyelitis (EAE). DAC treatment was associated with a significant amelioration of the clinical and histological hallmarks of EAE in both models. These effects were observed both in prophylactic and therapeutic regimens. The milder course of the disease was associated with a reduction in the number of spinal cord infiltrating lymphocytes and amelioration of the histopathological signs associated with EAE. In addition, increased transcript levels of anti‐inflammatory cytokines and decreased mRNA expression of pro‐inflammatory mediators were also observed. Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3. J. Cell. Physiol. 229: 1918–1925, 2014. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>