Hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models

Katia Mangano, Paolo Fagone, Klaus Bendtzen, Pier Luigi Meroni, Cinzia Quattrocchi, Santa Mammana, Michelino Di Rosa, Lucia Malaguarnera, Marinella Coco, Gaetano Magro, Roberto Di Marco, Ferdinando Nicoletti

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Abstract

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.

Original languageEnglish
Pages (from-to)1918-1925
Number of pages8
JournalJournal of Cellular Physiology
Volume229
Issue number12
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Mangano, K., Fagone, P., Bendtzen, K., Meroni, P. L., Quattrocchi, C., Mammana, S., Di Rosa, M., Malaguarnera, L., Coco, M., Magro, G., Di Marco, R., & Nicoletti, F. (2014). Hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models. Journal of Cellular Physiology, 229(12), 1918-1925. https://doi.org/10.1002/jcp.24641