Tesis doctoral de Beatriz Moreno Bruna
Titulo: efectos y mecanismos de acción de la metiltioadenosima en las enfermedades autoinmunes resumen: effects and mechanisms of action of methylthioadenosine in autoimmune diseases objective: to assess the immunomodulatory activity of methylthioadenosine (mta) in rodent models of autoimmune diseases (experimental autoimmune encephalomyelitis, col1agen induced arthritis and autoimmune diabetes) and patients of multiple sclerosis (ms).Methods: we study the effect of intraperitoneal mta in the acute and chronic ease, arthritis and autoimmune diabetes models by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain and spinal cord. We study the immunomodulatory effect of mta in lymphocytes from eae animáis, and in pbmc from healthy controls and ms patients by assessing the proliferation assay, cytokine gene expression by real-time pcr and nf-κb modulation by western-blot. results: we found that mta prevenís acute eae and, more importantly, reverses chronic-relapsing eae. This compound also has a partial protection in the arthritis and autoimmune diabetes models. 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 signalling resulting in the prevention of innibitor of kappa b (iκb-a) degradation and in the impaired activation of nuclear factor kappa b (nf-κb) transcription factor. Indeed, mta suppressed the production of pro-inflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-α and inducible ni trie oxide synthase) and increased the production of anti-inflammatory cytokines (interleukin- 10).Conclusion: mta has a remarkable immunomodulatory activity and may be beneficial for ms and other autoimmune diseases
Datos académicos de la tesis doctoral «Efectos y mecanismos de acción de la metiltioadenosima en las enfermedades autoinmunes«
- Título de la tesis: Efectos y mecanismos de acción de la metiltioadenosima en las enfermedades autoinmunes
- Autor: Beatriz Moreno Bruna
- Universidad: Navarra
- Fecha de lectura de la tesis: 15/12/2005
Dirección y tribunal
- Director de la tesis
- Pablo Villoslada Diaz
- Tribunal
- Presidente del tribunal: valentin Cena callejo
- xavier Montalvan gairin (vocal)
- ignacio Javier Melero bermejo (vocal)
- José María Frade lópez (vocal)