Allameh Abdolamir, Ahmadi-Ashtiani Hamid Reza, Maleki Narges
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Basic Sciences, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, 1941933311, Iran.
Heliyon. 2020 Jun 8;6(6):e04149. doi: 10.1016/j.heliyon.2020.e04149. eCollection 2020 Jun.
N-acetylcysteine (NAC) as a glutathione inducer is known for its anti-inflammatory effects in inflammatory conditions. The aim of the present study was to know if supplementation of the culture medium with can improve anti-inflammatory activities of hepatocytes during their differentiation from mesenchymal stem cells (MSCs). For this, hepatic differentiation of MSCs was performed in culture medium supplemented with NAC and selected pro- and anti-inflammatory factors were monitored for two weeks. Treatment of the MSCs undergoing hepatic differentiation with NAC (0.1 and 1.0 mM) caused a significant (~5-fold) increase in proliferation rate of MSCs, whereas the rate of hepatic differentiation was declined in NAC-treated cells as compared to those untreated with NAC. Under these circumstances, NAC caused a significant increase in total glutathione in cell lysate during 2 weeks of differentiation as compared to untreated group. NAC-related increase in glutathione was associated with significant alterations in tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8 and IL-10 levels secreted in the culture medium. A substantial decrease in the IL-6, IL-8 and TNF-α levels in the culture medium supplemented with NAC was obvious in hepatocytes recovered 14 days after differentiation. In contrast, the secretary IL-10 was significantly increased as a result of NAC treatments. These data suggest that NAC supplementation can improve anti-inflammatory activities of the hepatocytes derived from MSCs. NAC function mediated by glutathione synthesis can also help in modulation of proliferation of the stem cells and their differentiation into hepatocyte-like cells.
N-乙酰半胱氨酸（NAC）作为一种谷胱甘肽诱导剂，以其在炎症状态下的抗炎作用而闻名。本研究的目的是了解在培养基中添加NAC是否能在间充质干细胞（MSC）向肝细胞分化过程中提高肝细胞的抗炎活性。为此，在添加NAC的培养基中进行MSC的肝分化，并对选定的促炎和抗炎因子进行了两周的监测。用NAC（0.1和1.0 mM）处理正在进行肝分化的MSC，导致MSC的增殖率显著提高（约5倍），而与未用NAC处理的细胞相比，用NAC处理的细胞的肝分化率下降。在这种情况下，与未处理组相比，NAC在分化的2周内导致细胞裂解物中总谷胱甘肽显著增加。NAC相关的谷胱甘肽增加与培养基中分泌的肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-8和IL-10水平的显著变化有关。在分化14天后回收的肝细胞中，添加NAC的培养基中IL-6、IL-8和TNF-α水平明显大幅下降。相反，由于NAC处理，分泌的IL-10显著增加。这些数据表明，补充NAC可以提高源自MSC的肝细胞的抗炎活性。由谷胱甘肽合成介导的NAC功能也有助于调节干细胞的增殖及其向肝细胞样细胞的分化。
