RESUMEN

Inflammatory signals present in demyelinated multiple sclerosis lesions affect the reparative remyelination process conducted by oligodendrocyte progenitor cells (OPCs). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 have differing effects on the viability and growth of OPCs, however the effects of IL-17A are largely unknown. Primary murine OPCs were stimulated with IL-17A and their viability, proliferation, and maturation were assessed in culture. IL-17A-stimulated OPCs exited the cell cycle and differentiated with no loss in viability. Expression of the myelin-specific protein, proteolipid protein, increased in a cerebellar slice culture assay in the presence of IL-17A. Downstream, IL-17A activated ERK1/2 within 15 min and induced chemokine expression in 2 days. These results demonstrate that IL-17A exposure stimulates OPCs to mature and participate in the inflammatory response.

Asunto(s)

Diferenciación Celular/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Oligodendroglía/efectos de los fármacos , Oligodendroglía/enzimología , Células Madre/efectos de los fármacos , Animales , Células Cultivadas , Cerebelo/citología , Cerebelo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inducido químicamente , Citometría de Flujo , Adyuvante de Freund/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteína Proteolipídica de la Mielina/genética , Glicoproteína Mielina-Oligodendrócito/toxicidad , Técnicas de Cultivo de Órganos , Fragmentos de Péptidos/toxicidad , Receptores de Interleucina-17/deficiencia , Receptores de Interleucina-17/genética , Células Madre/fisiología