Corilagin Interferes With Toll-Like Receptor 3-Mediated Immune Response in Herpes Simplex Encephalitis

Frontiers in Molecular Neuroscience

Shao-Jun Zhang¹  You-Qin Wang¹  Jia-Bin Zhou²  Lei Zhao³  Yuan-Jin Guo⁴  Lu-Jun Li⁵  Pan Liu⁵  Yu-Jie Wang⁶  Zhi-Lin Chen⁷ 

[1] Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, China;Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Neurosurgery, Affiliated Hospital of Jining Medical University and Shangdong Provincial Key Laboratory of Stem Cells and Neuro-Oncology, Jining, China;Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;;National &Renmin Hospital of Hubei University of Medicine, The Postgraduate Training Center of Jinzhou Medical University, Shiyan, China;School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China;

关键词: corilagin;    herpes simplex virus type 1;    inflammation;    signaling pathway;    toll-like receptor 3;   

DOI  :  10.3389/fnmol.2019.00083

来源: DOAJ

【 摘 要 】

Herpes simplex encephalitis (HSE) is the most common infectious disease of the central nervous system worldwide. However, the pathogenesis of HSE is not clear. Research has shown that the immune response mediated by the toll-like receptor 3 (TLR3) signaling pathway is essential to protect the central nervous system against herpes simplex virus (HSV) infection. However, an excessive immune response may cause tissue damage accompanied by pathological changes. The aim of this study was to explore the molecular mechanism via which corilagin controls HSE through the TLR3 signaling pathway in vitro and in vivo. Cells and mice were pre-treated with polyriboinosinic polyribocytidylic acid [poly(I:C)] or HSV type 1, and then treated with corilagin. After treatment, the mRNA and protein levels of TLR3, TLR-like receptor-associated interferon factor (TRIF), tumor necrosis factor (TNF) receptor type 1-associated DEATH domain protein (TRADD), TNF receptor-associated factor (TRAF) 3 and 6, nuclear factor-kappa-B (NF-κB) essential modulator (NEMO), P38, and interferon regulatory factor 3 (IRF3) were decreased. Interleukin-6 (IL-6), TNF-α, and type 1 interferon-β were also decreased. When TLR3 expression was silenced or increased, corilagin still inhibited the expression of TLR3 and its downstream mediators. Hematoxylin-eosin (HE) staining and immunohistochemical examinations of mouse brain tissues revealed that corilagin lessened the degree of brain inflammation. Altogether, these results suggest that corilagin may regulate the immune response in HSE and relieve inflammatory injury by interfering with the TLR3 signaling pathway.

【 授权许可】

Unknown