Ramezani Ali Akbari Khadijeh, Fathollahi Anwar, Hashemi Seyed Mahmoud, Pouriran Ramin, Yeganeh Farshid
Department of Immunology, School of Medicine, Shahid Behesti University of Medical Sciences, Tehran, Iran.
Iran J Immunol. 2020 Mar;17(1):41-51. doi: 10.22034/iji.2020.80293.
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.
To evaluate the enzymatic activity of DPP-IV/CD26 and APN/CD13 in MSC conditioned media (MSC-CM).
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.
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.
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.
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。
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。
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。
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。
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。