Xiao Ran, Li Shan, Cao Qian, Wang Xiuling, Yan Qiujin, Tu Xiaoning, Zhu Ying, Zhu Fan
Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, 430071, China.
Department of Integrated Medicine, Dongfeng Hospital, Hubei University of Medicine, Wuhan, 442000, China.
Virol Sin. 2017 Jun;32(3):216-225. doi: 10.1007/s12250-017-3997-4. Epub 2017 Jun 23.
Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.
人类内源性逆转录病毒W包膜蛋白(HERV-W env)在许多神经心理疾病如精神分裂症和多发性硬化症(MS)中起着关键作用。这些疾病伴有中枢神经系统(CNS)的免疫反应。小胶质细胞是脑炎症中的重要免疫细胞,可产生一种气体递质——一氧化氮(NO)。NO不仅在神经元细胞功能中起作用,还参与各种神经心理疾病的发病机制。在本研究中,我们报道了CHME-5小胶质细胞转染HERV-W env后NO生成增加。此外,HERV-W env增加了人诱导型一氧化氮合酶(hiNOS)的表达和功能,并增强了hiNOS的启动子活性。小胶质细胞迁移也增强。这些数据表明,HERV-W env可能通过调节诱导型一氧化氮合酶的表达,促进神经心理疾病中NO的生成和小胶质细胞迁移能力。本研究结果可能有助于确定治疗神经心理疾病(包括神经炎症性疾病、中风和神经退行性疾病)的新靶点。