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鞣花酸通过体外和体内激活 cGAS-STING 信号通路抑制人巨细胞病毒感染和复制。

Corilagin inhibits human cytomegalovirus infection and replication via activating the cGAS-STING signaling pathway in vitro and in vivo.

机构信息

Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113401. doi: 10.1016/j.intimp.2024.113401. Epub 2024 Oct 17.

DOI:10.1016/j.intimp.2024.113401
PMID:39423664
Abstract

AIM

The existence of human cytomegalovirus (HCMV) is extremely widespread, causing serious diseases in patients with low immune function. The purpose of this study is to explore the efficacy and mechanism of Corilagin in the control of CMV infection, in order to provide scientific basis for the control of CMV infection.

METHODS

Our study employed an animal model in Balb/c mice, infected with MCMV, alongside cellular models in HFF cells and THP-1 cells, stimulated with HCMV. The expression of cGAS-STING signaling pathway molecules was detected in liver tissue, lung tissue, serum, cells and cell supernatant. The liver function and histopathological changes of mice were evaluated.

RESULTS

In vivo and in vitro experiments showed that Corilagin significantly inhibits CMV levels and attenuates pathological damage in liver and lung tissues in vivo, and similarly inhibits viral load in cells in vitro. Corilagin promotes the expression levels of STING and its downstream molecules in vivo and in vitro. Inhibition/down-regulation of STING significantly promotes CMV replication, on the contrary, activation/up-regulation of STING inhibits CMV replication, and Corilagin also promotes the expression levels of molecules related to the cGAS-STING signaling pathway in the above cases.

CONCLUSION

Corilagin could effectively inhibit the infection and replication of CMV in vitro and in vivo, which may be through the activation of cGAS-STING signaling pathway.

摘要

目的

人巨细胞病毒(HCMV)的存在极其广泛,在免疫功能低下的患者中会引起严重疾病。本研究旨在探讨柯里拉京对 CMV 感染的控制作用及其机制,为控制 CMV 感染提供科学依据。

方法

本研究采用 Balb/c 小鼠感染 MCMV 的动物模型以及 HFF 细胞和 THP-1 细胞受 HCMV 刺激的细胞模型,检测肝组织、肺组织、血清、细胞及细胞上清液中 cGAS-STING 信号通路分子的表达情况,评估小鼠的肝功能和组织病理学变化。

结果

体内和体外实验表明,柯里拉京显著抑制 CMV 水平,并减轻体内肝和肺组织的病理损伤,同时抑制体外细胞中的病毒载量。柯里拉京在体内和体外均促进 STING 及其下游分子的表达水平。STING 的抑制/下调显著促进 CMV 复制,相反,STING 的激活/上调抑制 CMV 复制,而且柯里拉京在上述情况下还促进 cGAS-STING 信号通路相关分子的表达水平。

结论

柯里拉京可有效抑制 CMV 在体内外的感染和复制,这可能是通过激活 cGAS-STING 信号通路实现的。

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