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肿瘤坏死因子-α诱导的间充质干细胞通过增加转化生长因子-β和白细胞介素-10在抑制炎症中的作用。

The Role of TNF-α induced MSCs on Suppressive Inflammation by Increasing TGF-β and IL-10.

作者信息

Putra Agung, Ridwan Fatkhan Baitul, Putridewi Allisha Irwaniyanti, Kustiyah Azizah Retno, Wirastuti Ken, Sadyah Nur Anna Chalimah, Rosdiana Ika, Munir Delfitri

机构信息

Stem Cell and Cancer Research of Medical Faculty, UNISSULA, Semarang, Indonesia.

Departement of Biomedical Postgraduate of Medical Faculty, UNISSULA, Semarang, Indonesia.

出版信息

Open Access Maced J Med Sci. 2018 Oct 4;6(10):1779-1783. doi: 10.3889/oamjms.2018.404. eCollection 2018 Oct 25.

Abstract

BACKGROUND

Mesenchymal stem cells (MSCs) may serve as immunoregulators by producing various anti-inflammatory molecules. Under sufficient level of TNF-α, MSCs become activated and adopt immune-suppressive phenotype (MSCs type-2) by releasing various anti-inflammatory molecule including TGF-β and IL-10. However, the ability of MSC itself to produce IL-10 under TNF-α stimulation and the correlation of TGF-β production of MSCs to IL-10 level remains to be elucidated.

AIM

In this study, MSCs were activated with various TNF-α doses to determine the increase of IL-10 and TGF-β level as well as its correlation.

MATERIAL AND METHODS

This study used post-test only control group design, by using 3 study groups, consist of 1 control (C) and 2 treatments (T) (TNF-α = 5 and 10 ng/mL) with triplicate induced in MSC for 24 hours, then the levels of IL-10 and TGF-β were measured by using ELISA assay.

RESULTS

The results of this study showed a significant increase of TGF-β and IL-10 levels (p < 0.05) at TNF-α 5 and 10 ng/mL dose of TNF-α. Moreover, there was a significant negative correlation between TGF-β and IL-10 level on 5 and 10 ng/mL dose TNF-α treatment.

CONCLUSION

Based on our study, we conclude that the 5 ng/mL dose of TNF-α is a sufficient dose for MSCs to suppress the inflammatory milieu. The higher increase of TGF beta is due to the controlled inflammation by IL-10.

摘要

背景

间充质干细胞(MSCs)可通过产生多种抗炎分子发挥免疫调节作用。在肿瘤坏死因子-α(TNF-α)水平充足时,MSCs被激活并通过释放包括转化生长因子-β(TGF-β)和白细胞介素-10(IL-10)在内的多种抗炎分子呈现免疫抑制表型(2型MSCs)。然而,MSCs自身在TNF-α刺激下产生IL-10的能力以及MSCs产生TGF-β与IL-10水平的相关性仍有待阐明。

目的

本研究用不同剂量的TNF-α激活MSCs,以确定IL-10和TGF-β水平的升高情况及其相关性。

材料与方法

本研究采用仅后测对照组设计,设3个研究组,包括1个对照组(C)和2个处理组(T)(TNF-α浓度分别为5和10 ng/mL),每组一式三份对MSCs诱导24小时,然后用酶联免疫吸附测定法(ELISA)检测IL-10和TGF-β水平。

结果

本研究结果显示,TNF-α剂量为5和10 ng/mL时,TGF-β和IL-10水平显著升高(p<0.05)。此外,在TNF-α剂量为5和10 ng/mL的处理组中,TGF-β与IL-10水平呈显著负相关。

结论

基于本研究,我们得出结论,5 ng/mL剂量的TNF-α足以使MSCs抑制炎症环境。TGF-β升高幅度更大是由于IL-10对炎症的控制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af3f/6236029/2ef791ba64f7/OAMJMS-6-1779-g001.jpg

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