Endothelin-1 contributes to the development of virus-induced demyelinating disease

• Main Authors: Young-Hee Jin, Bongsu Kang, Hyun S. Kang, Chang-Sung Koh, Byung S. Kim
• Format: Article
• Language: English
• Published: BMC 2020-10-01
• Series: Journal of Neuroinflammation
• Subjects: CNS; EAE; TMEV; Endothelin-1; Demyelination
• Online Access: http://link.springer.com/article/10.1186/s12974-020-01986-z

Abstract Background Experimental autoimmune encephalitis (EAE) and virally induced demyelinating disease are two major experimental model systems used to study human multiple sclerosis. Although endothelin-1 level elevation was previously observed in the CNS of mice with EAE and viral demyelinating disease, the potential role of endothelin-1 in the development of these demyelinating diseases is unknown. Methods and results In this study, the involvement of endothelin-1 in the development and progression of demyelinating diseases was investigated using these two experimental models. Administration of endothelin-1 significantly promoted the progression of both experimental diseases accompanied with elevated inflammatory T cell responses. In contrast, administration of specific endothelin-1 inhibitors (BQ610 and BQ788) significantly inhibited progression of these diseases accompanied with reduced T cell responses to the respective antigens. Conclusions These results strongly suggest that the level of endothelin-1 plays an important role in the pathogenesis of immune-mediated CNS demyelinating diseases by promoting immune responses.