Human endogenous retrovirus W family envelope protein (HERV-W env) facilitates the production of TNF-α and IL-10 by inhibiting MyD88s in glial cells.
Human endogenous retrovirus W family envelope protein (HERV-W env) facilitates the production of TNF-α and IL-10 by inhibiting MyD88s in glial cells.
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人内源性逆转录病毒 W 家族包膜蛋白 (HERV-W env) 通过抑制神经胶质细胞中的 MyD88s 促进 TNF-α 和 IL-10 的产生。
DOI：
10.1007/s00705-020-04933-8
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发表时间：
2021
影响因子：
2.7
通讯作者：
通讯作者）
中科院分区：
文献类型：
--
作者：
Wang Xiuling;Wu Xiulin;Huang Jin;Li Haiyan;Yan Qiujin;Zhu Fan（朱帆;通讯作者）
人内源性逆转录病毒W家族包膜蛋白（HERV-W env）与多种神经和精神疾病相关，包括多发性硬化症（MS）和精神分裂症。临床研究已经证明了神经精神疾病中炎症异常和HERV-W env之间的共同联系。尽管如此，HERV-W env介导神经炎症的分子机制仍不清楚。在本研究中，我们发现HERV-W env在U251和A172细胞中显著增加TNF-α和IL-10的mRNA和蛋白水平。HERV-W env还诱导Toll样受体4（TLR 4）的显著增加。TLR 4基因的敲除可抑制HERV-W env诱导的TNF-α和IL-10的表达。HERV-W env的过表达导致MyD 88的上调，但引起MyD 88的减少。MyD 88 s过表达可抑制HERV-W env诱导的TNF-α和IL-10的表达。这些结果表明HERV-W env通过抑制胶质细胞MyD 88 s的产生而上调IL-10和TNF-α的表达。这项工作揭示了HERV-W env在神经精神疾病中的免疫发病机制。
Human endogenous retrovirus W family envelope protein (HERV-W env) is associated with several neurological and psychiatric disorders, including multiple sclerosis (MS) and schizophrenia. Clinical studies have demonstrated a common link between inflammatory abnormalities and HERV-W env in neuropsychiatric diseases. Nonetheless, the molecular mechanisms by which HERV-W env mediates neuroinflammation are still unclear. In this study, we found that HERV-W env significantly increased the mRNA and protein levels of TNF-α and IL-10 in U251 and A172 cells. HERV-W env also induced a notable increase in Toll-like receptor 4 (TLR4). Knockdown of TLR4 impaired the expressions of TNF-α and IL-10 induced by HERV-W env. Overexpression of HERV-W env led to the upregulation of MyD88 but caused a decrease in MyD88s. MyD88s overexpression suppressed the expressions of TNF-α and IL-10 induced by HERV-W env. These findings indicate that HERV-W env upregulates the expressions of IL-10 and TNF-α by inhibiting the production of MyD88s in glial cells. This work sheds light on the immune pathogenesis of HERV-W env in neuropsychiatric disorders.