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四神丸对实验性结肠炎小鼠Tfh细胞的调节作用

Regulatory Effect of Sishen Pill on Tfh Cells in Mice With Experimental Colitis.

作者信息

Liu Xue-Ke, Zhao Hai-Mei, Wang Hai-Yan, Ge Wei, Zhong You-Bao, Long Jian, Liu Duan-Yong

机构信息

Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

出版信息

Front Physiol. 2020 Jun 5;11:589. doi: 10.3389/fphys.2020.00589. eCollection 2020.

Abstract

The T follicular helper T (Tfh) cells play a significant role in the pathogenesis of inflammatory bowel disease (IBD), which is regulated by the Bcl-6/Blimp-1 pathway. Some studies have suggested that regulating activation of the Bcl-6/Blimp-1 pathway should be an effective method to treat IBD. Sishen Pill (SSP) has been used frequently to treat chronic colitis. Its mechanism is related to the downstream proteins in the Bcl-6/Blimp-1 pathway. However, it is unknown whether SSP regulates the function and differentiation of Tfh cells to treat IBD. In the present study, chronic colitis was induced by dextran sodium sulfate and treated with SSP for 7 days. SSP effectively treated chronic colitis, regulated the balance between Tfh10, Tfh17 and T follicular regulatory cells, while SSP increased the Blimp-1 level, inhibited expressions of Bcl-6, T-cell costimulator, programmed death (PD)-1 and PD-ligand 1 on the surface of Tfh cells. SSP inhibited activation of BcL-6, phosphorylated signal transducer and activator of transcription (p-STAT)3, signal lymphocyte activation molecule (SLAM)-associated protein but improved Blimp-1 and STAT3 expression in colonic tissues. The results indicated that SSP regulated the differentiation and function of Tfh cells to treat IBD, which was potentially related with inhibiting the Bcl-6/Blimp-1 pathway.

摘要

滤泡辅助性T(Tfh)细胞在炎症性肠病(IBD)的发病机制中起重要作用,其受Bcl-6/Blimp-1信号通路调控。一些研究表明,调节Bcl-6/Blimp-1信号通路的激活应是治疗IBD的有效方法。四神丸(SSP)常用于治疗慢性结肠炎。其作用机制与Bcl-6/Blimp-1信号通路的下游蛋白有关。然而,SSP是否通过调节Tfh细胞的功能和分化来治疗IBD尚不清楚。在本研究中,用葡聚糖硫酸钠诱导慢性结肠炎,并给予SSP治疗7天。SSP有效治疗慢性结肠炎,调节Tfh10、Tfh17和滤泡调节性T细胞之间的平衡,同时SSP提高Blimp-1水平,抑制Tfh细胞表面Bcl-6、T细胞共刺激分子、程序性死亡(PD)-1和PD配体1的表达。SSP抑制BcL-6、磷酸化信号转导和转录激活因子(p-STAT)3、信号淋巴细胞激活分子(SLAM)相关蛋白的激活,但改善结肠组织中Blimp-1和STAT3的表达。结果表明,SSP通过调节Tfh细胞的分化和功能来治疗IBD,这可能与抑制Bcl-6/Blimp-1信号通路有关。

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