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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Methylthioadenosine reverses brain autoimmune disease
Authors: Moreno, B. (Beatriz)
Hevia, H. (Henar)
Santamaria, M. (Mónica)
Sepulcre, J. (Jorge)
Muñoz, J. (Javier)
Garcia-Trevijano, E.R. (Elena R.)
Berasain, C. (Carmen)
Corrales, F.J. (Fernando José)
Avila, M.A. (Matías Antonio)
Villoslada, P. (Pablo)
Keywords: Encephalomyelitis, Autoimmune, Experimental/prevention & control
Immunologic Factors/therapeutic use
Multiple Sclerosis/drug therapy
Thionucleosides/therapeutic use
Issue Date: 2006
Publisher: Wiley-Blackwell
Publisher version: http://onlinelibrary.wiley.com/doi/10.1002/ana.20895/abstract
ISSN: 1531-8249
Citation: Moreno B, Hevia H, Santamaria M, Sepulcre J, Munoz J, Garcia-Trevijano ER, et al. Methylthioadenosine reverses brain autoimmune disease. Ann Neurol 2006 Sep;60(3):323-334.
Abstract
OBJECTIVE: To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis. METHODS: We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-kappaB modulation by Western blot. RESULTS: We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha) degradation and in the impaired activation transcription factor nuclear factor-kappaB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10). INTERPRETATION: MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.
Permanent link: http://hdl.handle.net/10171/21521
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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