Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells.

Abstract

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.

• Authors: Xiuling Wang, Zhongchun Liu, Peigang Wang, Shan Li, Jie Zeng, Xiaoning Tu, Qiujin Yan, Zheman Xiao, Mengxian Pan, Fan Zhu
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 67 Pg. 324-334 (Jan 2018) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 28928004 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Gene Products, env
• Pregnancy Proteins
• TLR3 protein, human
• Toll-Like Receptor 3
• syncytin
• C-Reactive Protein

Topics

• Adult
• Astrocytes (metabolism)
• C-Reactive Protein (metabolism)
• Endogenous Retroviruses (metabolism)
• Gene Products, env (blood, metabolism)
• HEK293 Cells
• Humans
• Microglia (metabolism)
• Pregnancy Proteins (blood, metabolism)
• Schizophrenia (blood)
• Signal Transduction
• Toll-Like Receptor 3 (metabolism)
• Young Adult