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槲皮素联合人脐带间充质干细胞对肿瘤坏死因子-α/干扰素-γ刺激的外周血单个核细胞Toll样受体3信号通路激活的调节作用

Quercetin Combined With Human Umbilical Cord Mesenchymal Stem Cells Regulated Tumour Necrosis Factor-α/Interferon-γ-Stimulated Peripheral Blood Mononuclear Cells Activation of Toll-Like Receptor 3 Signalling.

作者信息

Chen Guiling, Ye Yang, Cheng Ming, Tao Yi, Zhang Kejun, Huang Qiong, Deng Jingwen, Yao Danni, Lu Chuanjian, Huang Yu

机构信息

Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of National Institute of Stem Cell Clinical Research, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

出版信息

Front Pharmacol. 2020 Apr 24;11:499. doi: 10.3389/fphar.2020.00499. eCollection 2020.

Abstract

The beneficial effect of quercetin in rheumatic diseases is unclear. Studies have already confirmed that human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate some symptoms of rheumatoid arthritis (RA) by their immunosuppressive capacities. This study explored whether there are additive effects of quercetin and hUCMSCs on peripheral blood mononuclear cells (PBMCs) under simulated rheumatic conditions. hUCMSCs were pretreated with quercetin (10 μM) before coculture with TNF-α/IFN-γ-stimulated PBMCs at a ratio of 1:1 for 3 days. PBMC proliferation was inhibited, and the proportion of Th17 cells was shifted. These effects may be related to the effect of quercetin on functional molecules in hUCMSCs, including nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), interleukin 6 (IL-6) and Toll-like receptor-3 (TLR-3) and the Akt/IκB pathways. These results suggest that quercetin effectively promoted the immunoregulatory effect of hUCMSCs by inhibiting the Akt/IκB pathway, activating the Toll-like receptor-3 pathway, and regulating downstream cytokines.

摘要

槲皮素在风湿性疾病中的有益作用尚不清楚。研究已经证实,人脐带间充质干细胞(hUCMSCs)通过其免疫抑制能力缓解类风湿性关节炎(RA)的一些症状。本研究探讨了在模拟风湿条件下,槲皮素和hUCMSCs对外周血单个核细胞(PBMCs)是否存在相加作用。在与TNF-α/IFN-γ刺激的PBMCs以1:1的比例共培养3天之前,hUCMSCs用槲皮素(10μM)进行预处理。PBMC增殖受到抑制,Th17细胞比例发生改变。这些作用可能与槲皮素对hUCMSCs中功能分子的影响有关,包括一氧化氮(NO)、吲哚胺2,3-双加氧酶(IDO)、白细胞介素6(IL-6)和Toll样受体3(TLR-3)以及Akt/IκB信号通路。这些结果表明,槲皮素通过抑制Akt/IκB信号通路、激活Toll样受体3信号通路并调节下游细胞因子,有效促进了hUCMSCs的免疫调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d713/7194129/eb3c8f8ca227/fphar-11-00499-g001.jpg

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