Sulforaphane effectively inhibits HBV by altering Treg/Th17 immune balance and the MIF-macrophages polarizing axis <i>in vitro</i> and <i>in vivo</i>

作者全名："Xu, Ruqing; Wu, Yue; Xiang, Xia; Lv, Xiaoqin; He, Miao; Xu, Chang; Lai, Guoqi; Xiang, Tingxiu"

作者地址："[Xu, Ruqing; Xiang, Xia; Lv, Xiaoqin; He, Miao; Xu, Chang; Lai, Guoqi; Xiang, Tingxiu] Chongqing Med Univ, Lab Anim Ctr, Chongqing, Peoples R China; [Xiang, Tingxiu] Chongqing Univ, Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis & I, Chongqing 400030, Peoples R China; [Wu, Yue; Xiang, Tingxiu] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Lai, GQ; Xiang, TX (通讯作者)，Chongqing Med Univ, Lab Anim Ctr, Chongqing, Peoples R China."

来源：VIRUS RESEARCH

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001166839600001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：341

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：HBV; Sulforaphane; Immunomodulation; CBA/CaJ; MIF

摘要："Background: Hepatitis B virus (HBV) infection is a major public health problem. After HBV infection, viral antigens shift the immune balance in favor of viral escape. Sulforaphane (SFN) is a traditional Chinese medicine.It regulates multi-biological activities, including anti-inflammation, anticancer, and antiviral. However, few studies reported that SFN can inhibit HBV infection before. Methods: An immunocompetent HBV CBA/CaJ mouse model and a co-culture model were used to explore the effect of SFN on HBV and whether SFN altered the immune balance after HBV infection. Results: We found that SFN was able to reduce HBV DNA, cccDNA, HBsAg, HBeAg, and HBcAg levels in serum and liver tissues of HBV-infected mice. In vitro and in vivo experiments showed that SFN could significantly increase the expression of Cd86 and iNOS and inhibit the expression of Arg1 on macrophages after HBV infection. After SFN administration, Th17 markers in liver tissue and serum were significantly increased. There was no significant changes in the proportion of Treg cells in peripheral blood, but a significant increase in the proportion of Th17 cells and decrease of the Treg/Th17 ratio. Using a network pharmacology approach, we predicted macrophage migration inhibitory factor (MIF) as a potential target of SFN and further validated that MIF expression was significantly increased after HBV infection and SFN significantly inhibited MIF expression both in vitro and in vivo. There was an upward trend in HBV markers (p>0.05) after MIF overexpression. Overexpression of MIF combined with the use of SFN resulted in a significant reversion in the expression of HBV markers and polarization of macrophages towards the M1 phenotype. Conclusion: Our results indicated that immunocompetent HBV CBA/CaJ mouse model is a good model to evaluate HBV infection. SFN could inhibit the expression of HBV markers, promote polarization of macrophages towards the M1 phenotype after HBV infection, change the proportion of Treg and Th17 cells. Our findings demonstrate that SFN inhibit HBV infection by inhibiting the expression of MIF and promoting the polarization of macrophages towards the M1 phenotype, which illustrates a promising therapeutic approach in HBV infection."

基金机构：National Natural Science Foundation of China [82172619]; Min-Sheng Project of Chongqing Science and Technology [cstc2017shmsA 130097]; Chongqing Postgraduate Innovation Project in Scientific Research [CYS 21243]

基金资助正文："This work was supported by the National Natural Science Foundation of China [grant number 81570 541] , the Min-Sheng Project of Chongqing Science and Technology [grant number cstc2017shmsA 130097] , the Chongqing Postgraduate Innovation Project in Scientific Research [grant number CYS 21243] , and the National Natural Science Foundation of China [grant number 82172619] ."