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Hypomethylating Agent 5‐Aza‐2′‐deoxycytidine (DAC) Ameliorates Multiple Sclerosis in Mouse Models
Author(s) -
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
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24641
Subject(s) - experimental autoimmune encephalomyelitis , foxp3 , context (archaeology) , epigenetics , multiple sclerosis , deoxycytidine , hypomethylating agent , immunology , medicine , pharmacology , encephalomyelitis , cancer research , dna methylation , biology , cancer , gene expression , immune system , gene , paleontology , biochemistry , gemcitabine
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.