Chenari Abolfazl, Hazrati Ali, Hosseini Ahmad Zavaran, Motiee Mahdieh, Soudi Sara
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Life Sci. 2023 Mar 15;317:121465. doi: 10.1016/j.lfs.2023.121465. Epub 2023 Jan 31.
Mesenchymal stem cells (MSCs) are among the known cells that can control and modulate immune responses in different circumstances, including autoimmune diseases. Also, various studies have shown that they can prevent and reduces the pulmonary inflammation caused by infectious agents. In the case of tuberculosis and inflammation caused by BCG, the granuloma has destructive effects and improper orientation of the immune response. Therefore, it is possible to prevent airway damage by preventing harmful inflammatory responses and guiding the immune system responses. This study investigates the role of nasal administration of MSCs supernatant by designing an inflammatory model in the BALB/c mice lung with BCG. MSCs are isolated from mice adipose tissue in this study and evaluated for their phenotypic and differentiation properties. After the third passage, these cells' condition medium (CM) was collected. 20 mice were divided into four groups. Group 1 receive BCG (10 CFU in 5 ml volume for 15 min) nasal administration. Group 2 treated with CM, and group 3 initially were treated with CM (in 5 ml volume for 15 min) and, after 24 h, treated with BCG nasal administration. CM treatment was continued every five days for one month. The fourth group of mice was treated with PBS nasal administration of CM and BCG. One week after the last administration, the lung tissue of mice in each group was pathologically examined. In addition, secretion of IL1-β, IL-6, TNF-α, TGF-β, and IL-10 in the alveolar fluid and secretion of IL-4 and IFN-γ cytokines in the supernatant of splenocytes was evaluated by ELISA. The TNF-α/IL-10 ratio in the alveolar lung fluid of the BCG received group is 2/9 and decreased to 0.58 after successive CM treatment. Therefore, it can be concluded that inflammatory responses to BCG infection in the presence of CM are balanced and pave the way for the induction of effective immune responses by reducing lung tissue damage.
间充质干细胞（MSCs）是已知的能够在不同情况下控制和调节免疫反应的细胞之一，包括自身免疫性疾病。此外，各种研究表明，它们可以预防和减轻由感染因子引起的肺部炎症。在结核病和卡介苗引起的炎症病例中，肉芽肿具有破坏作用且免疫反应方向不当。因此，通过预防有害的炎症反应并引导免疫系统反应，有可能预防气道损伤。本研究通过在BALB/c小鼠肺部设计卡介苗炎症模型，研究鼻内给予间充质干细胞上清液的作用。在本研究中，从小鼠脂肪组织中分离间充质干细胞，并对其表型和分化特性进行评估。在第三次传代后，收集这些细胞的条件培养基（CM）。将20只小鼠分为四组。第1组接受卡介苗（5毫升体积中含10个菌落形成单位，持续15分钟）鼻内给药。第2组用条件培养基处理，第3组最初用条件培养基（5毫升体积，持续15分钟）处理，24小时后进行卡介苗鼻内给药。每五天继续进行条件培养基处理，持续一个月。第四组小鼠用PBS鼻内给予条件培养基和卡介苗。在最后一次给药一周后，对每组小鼠的肺组织进行病理检查。此外，通过酶联免疫吸附测定法评估肺泡液中白细胞介素1-β、白细胞介素6、肿瘤坏死因子-α、转化生长因子-β和白细胞介素10的分泌，以及脾细胞上清液中白细胞介素4和干扰素-γ细胞因子的分泌。接受卡介苗组的肺泡肺液中肿瘤坏死因子-α/白细胞介素10的比值为2/9，在连续条件培养基处理后降至0.58。因此，可以得出结论，在存在条件培养基的情况下，对卡介苗感染的炎症反应是平衡的，通过减少肺组织损伤为诱导有效的免疫反应铺平了道路。
