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. 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. 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.

中文翻译：

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Endothelin-1 有助于病毒诱导的脱髓鞘疾病的发展

实验性自身免疫性脑炎 (EAE) 和病毒性脱髓鞘疾病是用于研究人类多发性硬化症的两个主要实验模型系统。尽管之前在患有 EAE 和病毒性脱髓鞘疾病的小鼠的 CNS 中观察到内皮素 1 水平升高，但内皮素 1 在这些脱髓鞘疾病发展中的潜在作用尚不清楚。在这项研究中，使用这两个实验模型研究了内皮素-1 在脱髓鞘疾病的发展和进展中的参与。内皮素-1 的给药显着促进了两种实验疾病的进展，并伴有炎症 T 细胞反应的升高。相比之下，使用特定的内皮素-1 抑制剂（BQ610 和 BQ788）可显着抑制这些疾病的进展，同时降低 T 细胞对相应抗原的反应。这些结果有力地表明，内皮素-1 的水平通过促进免疫反应在免疫介导的中枢神经系统脱髓鞘疾病的发病机制中起重要作用。