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脂多糖和佛波酯处理后间充质干细胞分泌组中二肽基肽酶-IV/CD26和氨肽酶N/CD13的活性

Activity of Dipeptidyl Peptidase-IV/CD26 and Aminopeptidase N/CD13 in Secretome of Mesenchymal Stem Cells after Treatment with LPS and PMA.

作者信息

Ramezani Ali Akbari Khadijeh, Fathollahi Anwar, Hashemi Seyed Mahmoud, Pouriran Ramin, Yeganeh Farshid

机构信息

Department of Immunology, School of Medicine, Shahid Behesti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Immunol. 2020 Mar;17(1):41-51. doi: 10.22034/iji.2020.80293.

Abstract

BACKGROUND

Emerging evidence suggests that secretome of mesenchymal stem cells has many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of autoimmune and degenerative diseases. Dipeptidyl Peptidase-IV (DPP-IV)/CD26 and Aminopeptidase N (APN)/CD13 are ubiquitous ecto-enzymes which can digest various substrates including some chemokines and neuropeptides that are involved in inflammatory conditions.

OBJECTIVE

To evaluate the enzymatic activity of DPP-IV/CD26 and APN/CD13 in MSC conditioned media (MSC-CM).

METHODS

The MSCs were isolated from the mouse's abdominal adipose tissues and were cultured with or without preconditioning by adding phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). The levels of interleukin-10 (IL-10), nitric oxide (NO), as well as the enzymatic activities of DPP-IV/CD26 and APN/CD13 were measured in MSC-CM.

RESULTS

The level of IL-10 and the enzyme activity of APN/CD13 did not show any changes in the MSC-CM of stimulated and non-stimulated cells. However, NO production was increased after treatment by LPS or PMA; nevertheless, the DPP-IV/CD26 activity was decreased in MSC-CM merely following the stimulation of cells with LPS.

CONCLUSION

Our results indicated that MSC-secretome had DPP-IV/CD26 and APN/CD13 activity. The DPP-IV/CD26 activity was decreased following stimulation of MSCs by toll-like receptor 4 agonist. Further studies are needed to reveal the possible contribution of DPP-IV/CD26 and APN/CD13 in the anti-inflammatory functions of MSC-CM.

摘要

背景

新出现的证据表明,间充质干细胞的分泌组具有多种抗炎和再生特性,这使其成为治疗自身免疫性疾病和退行性疾病的合适候选者。二肽基肽酶-IV(DPP-IV)/CD26和氨肽酶N(APN)/CD13是普遍存在的胞外酶,它们可以消化各种底物,包括一些参与炎症反应的趋化因子和神经肽。

目的

评估间充质干细胞条件培养基(MSC-CM)中DPP-IV/CD26和APN/CD13的酶活性。

方法

从小鼠腹部脂肪组织中分离间充质干细胞,并在添加佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)或脂多糖(LPS)预处理或不预处理的情况下进行培养。检测MSC-CM中白细胞介素-10(IL-10)、一氧化氮(NO)水平以及DPP-IV/CD26和APN/CD13的酶活性。

结果

在刺激和未刺激细胞的MSC-CM中,IL-10水平和APN/CD13的酶活性均未显示任何变化。然而,LPS或PMA处理后NO产生增加;尽管如此,仅在用LPS刺激细胞后,MSC-CM中的DPP-IV/CD26活性降低。

结论

我们的结果表明,MSC分泌组具有DPP-IV/CD26和APN/CD13活性。Toll样受体4激动剂刺激间充质干细胞后,DPP-IV/CD26活性降低。需要进一步研究以揭示DPP-IV/CD26和APN/CD13在MSC-CM抗炎功能中的可能作用。

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