Özdemir Alper Tunga, Nalbantsoy Ayşe, Özgül Özdemir Rabia Bilge, Berdeli Afig
Ege University, Institute of Health Sciences, Department of Stem Cell, Izmir, Turkey.
Manisa City Hospital, Allergy and Clinical Immunology Clinic, Manisa, Turkey.
Prostaglandins Other Lipid Mediat. 2022 Apr;159:106610. doi: 10.1016/j.prostaglandins.2021.106610. Epub 2021 Dec 25.
15-lipoxygenase (15-LOX) is a critical enzyme that allows the direction of arachidonic acid metabolism to change from inflammation into the resolution. This study aims to reveal how the immunomodulation properties of mesenchymal stem cells (MSC) alter by the 15-LOX overexpression. For this purpose, peripheral blood mononuclear cells (PBMCs) isolated from seven healthy volunteers, and both MSCs and 15-LOX overexpressing MSCs (MSCs) were co-cultured at different cell ratios (1/1, 1/5 and 1/10). Alterations of CD4Tbet, CD4Gata3, CD4RoRC2, and CD4FoxP3 lymphocyte frequencies were detected by flow cytometry, and IFN-γ, IL-4, IL-6, IL-10, IL-17a, TGF-β and LXA levels of medium supernatants were measured by ELISA method. According to our findings, MSC and MSCs have a suppressive effect on PHA activated PBMCs. However, as the ratio of PBMCs increased, the effects of MSCs increased significantly, while the effects of MSCs decreased. The most notable effect of the 15-LOX modification was the significant reduction in IL-6, IL-10 and IL-17a expression and the accompanying increase in TGF-β and LXA levels. We also observed a similar situation between CD4RoRC2 and CD4FoxP3 cell frequencies. These data suggested that the effects of MSCs on the balance of Th17 / Treg could change by the 15-LOX overexpression, and this might be in favor of the Treg cells.
15-脂氧合酶（15-LOX）是一种关键酶，它能使花生四烯酸代谢方向从炎症转变为炎症消退。本研究旨在揭示间充质干细胞（MSC）的免疫调节特性如何因15-LOX过表达而改变。为此，从7名健康志愿者中分离出外周血单个核细胞（PBMC），并将MSC和15-LOX过表达的MSC（MSCs）以不同细胞比例（1/1、1/5和1/10）进行共培养。通过流式细胞术检测CD4Tbet、CD4Gata3、CD4RoRC2和CD4FoxP3淋巴细胞频率的变化，并用ELISA法测定培养基上清液中IFN-γ、IL-4、IL-6、IL-10、IL-17a、TGF-β和LXA的水平。根据我们的研究结果，MSC和MSCs对PHA激活的PBMC具有抑制作用。然而，随着PBMC比例的增加，MSCs的作用显著增强，而MSCs的作用减弱。15-LOX修饰最显著的作用是IL-6、IL-10和IL-17a表达显著降低，同时TGF-β和LXA水平相应升高。我们还观察到CD4RoRC2和CD4FoxP3细胞频率之间存在类似情况。这些数据表明，15-LOX过表达可能会改变MSCs对Th17/Treg平衡的影响，这可能有利于调节性T细胞。
