Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells
Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells
复制标题
Syncytin-1 是一种内源性逆转录病毒蛋白，通过神经胶质细胞中的 TLR3 信号级联触发 CRP 的激活
DOI：
10.1016/j.bbi.2017.09.009
复制
发表时间：
2018-01-01
影响因子：
15.1
通讯作者：
Zhu, Fan
中科院分区：
文献类型：
--
作者：
Wang, Xiuling;Liu, Zhongchun;Zhu, Fan
精神分裂症是一种破坏性的精神疾病，影响社会功能和生活质量，并且有越来越多的证据表明炎症是精神分裂症的潜在致病机制。然而，精神分裂症可能发生的炎症机制尚未得到很好的理解。内源性逆转录病毒蛋白syncytin-1和炎症标志物CRP在精神分裂症患者中均异常表达。CRP通常是细菌感染的标志物之一。不太清楚的是病毒或病毒蛋白是否可以触发CRP的激活。在这里，我们检测到一个强大的增加syncytin-1和CRP的水平在精神分裂症患者，并显示了正相关和显着的一致性syncytin-1和CRP的表达在精神分裂症患者之间。此外，合胞素-1的过度表达显著升高了人小胶质细胞和星形胶质细胞中CRP、TLR 3和IL-6的水平。TLR 3缺乏可抑制syncytin-1诱导的CRP和IL-6的表达。重要的是，我们观察到细胞共定位和合胞素-1和TLR 3之间的直接相互作用。此外，IL-6的敲低抑制合胞素-1诱导的CRP表达。因此，这些结果的总体表明，病毒蛋白合胞素-1可以触发CRP的激活，这可能解释了无菌性炎症中CRP的升高，并显示出合胞素-1在精神分裂症中调节炎症的新机制。(C)2017爱思唯尔公司All rights reserved.
Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP. Here, we detected a robust increase of the levels of syncytin-1 and CRP in schizophrenia patients, and displayed a positive correlation and marked consistency between expressions of syncytin-1 and CRP in schizophrenia patients. Furthermore, overexpression of syncytin-1 significantly elevated the levels of CRP, TLR3, and IL-6 in both human microglia and astrocytes. TLR3 deficiency impaired the expressions of CRP and IL-6 induced by syncytin-1. Importantly, we observed a cellular co-localization and a direct interaction between syncytin-1 and TLR3. Additionally, knockdown of IL-6 inhibited the syncytin-1-induced CRP expression. Thus, the totality of these results showed that viral protein syncytin-1 could trigger the activation of CRP, which might explain the elevated CRP in sterile inflammation and exhibit a novel mechanism for regulation of inflammation by syncytin-1 in schizophrenia. (C) 2017 Elsevier Inc. All rights reserved.