MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating theiler murine encephalomyelitis.

Ulrich, Reiner; Baumgärtner, Wolfgang; Gerhauser, Ingo; Seeliger, Frank; Haist, Verena; Deschl, Ulrich; Alldinger, Susanne

Ulrich, Reiner; Baumgärtner, Wolfgang; Gerhauser, Ingo; Seeliger, Frank; Haist, Verena; Deschl, Ulrich; Alldinger, Susanne.

Afiliación

Ulrich R; Department of Pathology, University of Veterinary Medicine Hannover, Germany.

J Neuropathol Exp Neurol ; 65(8): 783-93, 2006 Aug.

Article en En | MEDLINE | ID: mdl-16896312

RESUMEN

Theiler murine encephalomyelitis (TME) represents a highly relevant viral model for multiple sclerosis. Matrix metalloproteinases (MMPs) degrade extracellular matrix molecules and are involved in demyelination processes. To elucidate their impact on demyelination in TME, spinal cords of TME virus (TMEV)-infected SJL/J mice were taken at 9 different time points postinfection (pi) ranging from 1 hour to 196 days pi and investigated for the expression of TMEV, MMP-2, -3, -7, -9, -10, -11, -12, -13, -14, -15, -24, and TIMP-1 to -4 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). High TMEV RNA levels were detectable throughout the observation period using RT-qPCR. In addition, TMEV RNA was visualized within demyelinated lesions by in situ hybridization. MMP-3 mRNA was significantly upregulated at 1 day pi and again in the late phase of infection. TIMP-1 mRNA was significantly elevated throughout the observation period. MMP-12 mRNA was most prominently upregulated in the late phase of infection and MMP-12 protein was localized in intralesional microglia/macrophages and astrocytes by immunohistochemistry. In summary, in early TMEV infection, MMP-3 and TIMP-1 mRNA upregulation might be directly virus-induced, whereas persistent TMEV infection directly or indirectly stimulated MMP-12 production in microglia/macrophages and astrocytes and might account for ongoing demyelination in TME.

Asunto(s)

Infecciones por Cardiovirus/enzimología; Enfermedades Desmielinizantes/enzimología; Encefalomielitis/enzimología; Metaloproteinasas de la Matriz/metabolismo; Theilovirus/genética; Inhibidor Tisular de Metaloproteinasa-1/metabolismo; Animales; Infecciones por Cardiovirus/genética; Infecciones por Cardiovirus/patología; Sistema Nervioso Central/enzimología; Sistema Nervioso Central/patología; Sistema Nervioso Central/fisiopatología; Enfermedad Crónica; Enfermedades Desmielinizantes/genética; Enfermedades Desmielinizantes/virología; Modelos Animales de Enfermedad; Encefalomielitis/genética; Encefalomielitis/virología; Femenino; Regulación Enzimológica de la Expresión Génica/genética; Macrófagos/metabolismo; Metaloproteinasa 12 de la Matriz; Metaloproteinasa 3 de la Matriz/metabolismo; Metaloendopeptidasas/metabolismo; Ratones; Microglía/metabolismo; Esclerosis Múltiple/enzimología; Esclerosis Múltiple/genética; Esclerosis Múltiple/fisiopatología; Vaina de Mielina/metabolismo; Vaina de Mielina/patología; ARN Mensajero/análisis; ARN Mensajero/genética; ARN Viral/análisis; ARN Viral/genética; Factores de Tiempo; Regulación hacia Arriba; Carga Viral

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Desmielinizantes / Theilovirus / Infecciones por Cardiovirus / Inhibidor Tisular de Metaloproteinasa-1 / Metaloproteinasas de la Matriz / Encefalomielitis Tipo de estudio: Prognostic_studies Idioma: En Revista: J Neuropathol Exp Neurol Año: 2006 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

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