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飞燕草素-3-O-葡萄糖苷在体外抑制 NF-κB 并改变间充质干细胞的分泌组,从而影响巨噬细胞的激活。

Delphinidin-3-O-glucoside in vitro suppresses NF-κB and changes the secretome of mesenchymal stem cells affecting macrophage activation.

机构信息

Department of Clinical and Toxicologic Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil.

出版信息

Nutrition. 2023 Jan;105:111853. doi: 10.1016/j.nut.2022.111853. Epub 2022 Sep 30.

DOI:10.1016/j.nut.2022.111853
PMID:36335873
Abstract

OBJECTIVE

Anthocyanins are polyphenols that are promising chemopreventive agents. They stand out for their anti-inflammatory properties, with specific modulatory actions on the immune system. Additionally, regarding the immune system, a group of cells identified as mesenchymal stem cells (MSCs) have been attracting attention, mainly because of their capacity to migrate to sites of inflammation and produce potent immunomodulatory effects. Considering the ability of these cells to act on the immune system, as well as the properties of anthocyanins, especially delphinidin, in modulating the immune system, the aim of this study was to investigate the effects of delphinidin in influencing some immunoregulatory properties of MSCs.

METHODS

MSCs were cultivated in the presence of delphinidin 3-O-β-d-glycoside and cell viability, the cell cycle and the production of soluble factors (interleukin [IL]-1β, IL-6, IL-10, transforming growth factor [TGF]-β, prostaglandin E [PGE] and nitric oxide [NO]) were evaluated, as was the expression of the transcription factors nuclear factor (NF)-κB and STAT3. Additionally, the effects of conditioned media from MSCs on macrophage activation were assessed.

RESULTS

Delphinidin at 50 µM does not affect cell viability. In association with lipopolysaccharide, delphinidin was able to induce MSC proliferation. Additionally, delphinidin modulated the MSC immune response, showing increased levels of anti-inflammatory cytokines such as IL-10 and TGF-β as well as lower expression of NF-κB. Furthermore, conditioned media from MSCs inhibited macrophage metabolism, reducing the production of IL-1β, IL-12, and TNF-α and increasing IL-10.

CONCLUSIONS

Overall, this work showed that delphinidin can modify the immunomodulatory properties of MSCs, increasing the IL-10 production by macrophages.

摘要

目的

花色苷是具有潜在化学预防作用的多酚类化合物。它们具有抗炎特性,对免疫系统具有特定的调节作用。此外,一组被鉴定为间充质干细胞(MSCs)的细胞引起了人们的关注,主要是因为它们能够迁移到炎症部位并产生有效的免疫调节作用。鉴于这些细胞对免疫系统的作用能力,以及花色苷(尤其是飞燕草素)调节免疫系统的特性,本研究旨在探讨飞燕草素对 MSCs 一些免疫调节特性的影响。

方法

在存在飞燕草素 3-O-β-d-糖苷的情况下培养 MSCs,并评估细胞活力、细胞周期以及可溶性因子(白细胞介素 [IL]-1β、IL-6、IL-10、转化生长因子 [TGF]-β、前列腺素 E [PGE] 和一氧化氮 [NO])的产生,以及转录因子核因子(NF)-κB 和 STAT3 的表达。此外,还评估了 MSC 条件培养基对巨噬细胞激活的影响。

结果

50μM 的飞燕草素不会影响细胞活力。与脂多糖联合使用时,飞燕草素能够诱导 MSC 增殖。此外,飞燕草素调节 MSC 的免疫反应,表现为抗炎细胞因子如 IL-10 和 TGF-β的水平升高,以及 NF-κB 的表达降低。此外,MSC 条件培养基抑制了巨噬细胞代谢,减少了 IL-1β、IL-12 和 TNF-α的产生,增加了 IL-10 的产生。

结论

总体而言,这项工作表明飞燕草素可以改变 MSCs 的免疫调节特性,增加巨噬细胞产生的 IL-10。

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