Hypomethylating agent 5-aza-2'-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models.
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.
Department of Bio-medical Sciences, University of Catania, Via Androne, Catania (CT), Italy.
Katia
K
Mangano
Paolo
P
Fagone
Klaus
K
Bendtzen
Pier Luigi
PL
Meroni
Cinzia
C
Quattrocchi
Santa
S
Mammana
Michelino
M
Di Rosa
Lucia
L
Malaguarnera
Marinella
M
Coco
Gaetano
G
Magro
Roberto
R
Di Marco
Ferdinando
F
Nicoletti
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016207:Cytokines / Q000378:metabolism; D000077209:Decitabine; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D000077209:Decitabine; D001374:Azacitidine