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枸杞多糖通过 Toll 样受体 4-Erk1/2-Blimp1 信号通路促进小鼠树突状细胞成熟。

Lycium barbarum Polysaccharides Promote Maturity of Murine Dendritic Cells through Toll-Like Receptor 4-Erk1/2-Blimp1 Signaling Pathway.

机构信息

Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.

Department of Laboratory Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, China.

出版信息

J Immunol Res. 2020 Dec 1;2020:1751793. doi: 10.1155/2020/1751793. eCollection 2020.

Abstract

In previous studies, Lycium barbarum polysaccharides (LBP), a traditional Chinese medicine, can promote immature dendritic cells (DCs) to mature. However, the molecular mechanisms by which LBP works are not yet elucidated. Here, we found that LBP can induce DCs maturation, which is mainly characterized by the upregulation of MHCII and costimulatory molecules (CD80, CD86), and increase the production of IL-6 and IL-4. Furthermore, we found that LBP could increase the mRNA and protein expression of TLR4, p38, Erk1/2, JNK, and Blimp1 signal molecules. More interestingly, after blocking by Toll-like receptor 4 inhibitor, Resatorvid (TAK 242), the mRNA and protein expression of TLR4, Erk1/2, and Blimp1 was significantly decreased while the expression of p38 and JNK has not changed. Then, we found that after blocking by p38 inhibitor (SB203580), Erk inhibitor (PD98059), and JNK inhibitor (SP603580) separately, Blimp1 protein expression was significantly reduced; after downregulating Blimp1 by Blimp1-siRNA, the production of IL-6 was reduced. In conclusion, our results indicate that LBP can induce maturation of DCs through the TLR4-Erk1/2-Blimp1 signal pathway instead of the JNK/p38-Blimp1 pathway. Our findings may provide a novel evidence for understanding the molecular mechanisms of LBP on activating murine DCs.

摘要

在以前的研究中,枸杞多糖(LBP)作为一种中药,可以促进未成熟树突状细胞(DCs)成熟。然而,LBP 的作用机制尚不清楚。在这里,我们发现 LBP 可以诱导 DCs 成熟,其主要特征是 MHCII 和共刺激分子(CD80、CD86)的上调,并增加 IL-6 和 IL-4 的产生。此外,我们发现 LBP 可以增加 TLR4、p38、Erk1/2、JNK 和 Blimp1 信号分子的 mRNA 和蛋白表达。更有趣的是,在用 Toll 样受体 4 抑制剂 Resatorvid(TAK 242)阻断后,TLR4、Erk1/2 和 Blimp1 的 mRNA 和蛋白表达显著降低,而 p38 和 JNK 的表达没有变化。然后,我们发现在用 p38 抑制剂(SB203580)、Erk 抑制剂(PD98059)和 JNK 抑制剂(SP603580)分别阻断后,Blimp1 蛋白表达显著降低;用 Blimp1-siRNA 下调 Blimp1 后,IL-6 的产生减少。总之,我们的结果表明,LBP 可以通过 TLR4-Erk1/2-Blimp1 信号通路而不是 JNK/p38-Blimp1 通路诱导 DCs 成熟。我们的发现可能为理解 LBP 激活小鼠 DCs 的分子机制提供新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b0/7725586/74c0dd3e38b0/JIR2020-1751793.001.jpg

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