Hypomethylating agent 5-aza-2'-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models.

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.

• Authors: 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
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 229 Issue 12 Pg. 1918-25 (Dec 2014) ISSN: 1097-4652 [Electronic] United States
• PMID: 24700487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Decitabine
• Azacitidine

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, adverse effects)
• Azacitidine (administration & dosage, analogs & derivatives)
• Cytokines (metabolism)
• Decitabine
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, genetics, pathology)
• Mice
• Multiple Sclerosis (genetics, pathology)
• T-Lymphocytes, Regulatory