Department of Clinical and Toxicologic Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil.
Nutrition. 2020 Oct;78:110935. doi: 10.1016/j.nut.2020.110935. Epub 2020 Jul 4.
The essential branched chain amino acids (BCAAs) valine, leucine, and isoleucine, are widely studied because of their effects on immunity and metabolism. Mesenchymal stem cells (MSCs) are a type of cell also studied due to their immunomodulatory properties. Since both BCAAs and MSCs have immunomodulatory capacity, the objective of this study was to evaluate the influence of BCAAs on some immunomodulatory aspects of MSCs.
MSCs were cultivated in BCAA-supplemented media to evaluate metabolic activity, including cell cycle, proliferative nuclear cell antigen, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, avian myelocytomatosis viral oncogene homolog, peroxisome proliferator activated receptor gamma, nuclear factor kappa B (NFкB), and signal transducers and activators of transcription 3 (STAT-3) expression. Additionally, some inflammatory mediators' synthesis, such as interleukin (IL) 1-beta, IL-10, granulocyte-macrophage colony-stimulating factor, transforming growth factor beta, nitric oxide, and prostaglandin E, were also evaluated.
Supplementation with BCAA led not only to increased MSC proliferation with more cells in the S, G2, and M cycle phases, but also to increased metabolic activity. BCAA supplementation also altered the immunomodulatory capacity of MSCs by decreasing the p-NFкB/NFкB and increasing the p-STAT-3/STAT-3 gene expression ratios, in addition to increasing synthesis of the antiinflammatory mediators transforming growth factor beta and prostaglandin E. Finally, MSCs cultivated in BCAA-supplemented media was shown to decrease the IL-6 and tumor necrosis factor alpha production by macrophages.
BCAA supplementation affected some immunoregulatory aspects of MSCs.
支链氨基酸（BCAAs）亮氨酸、异亮氨酸和缬氨酸是研究热点，因为它们对免疫和代谢有影响。间充质干细胞（MSCs）因其免疫调节特性也在研究之列。由于 BCAAs 和 MSCs 都具有免疫调节能力，本研究旨在评估 BCAAs 对 MSCs 某些免疫调节方面的影响。
在补充 BCAAs 的培养基中培养 MSCs，以评估代谢活性，包括细胞周期、增殖细胞核抗原、过氧化物酶体增殖物激活受体γ共激活因子 1-α、禽髓细胞瘤病毒癌基因同源物、过氧化物酶体增殖物激活受体 γ、核因子 kappa B（NFкB）和信号转导子和转录激活子 3（STAT-3）的表达。此外，还评估了一些炎症介质的合成，如白细胞介素（IL）1-β、IL-10、粒细胞-巨噬细胞集落刺激因子、转化生长因子-β、一氧化氮和前列腺素 E。
BCAA 补充不仅导致 MSC 增殖增加，S、G2 和 M 期细胞增多，而且代谢活性增加。BCAA 补充还通过降低 p-NFкB/NFкB 并增加 p-STAT-3/STAT-3 基因表达比值，改变 MSCs 的免疫调节能力，此外还增加抗炎介质转化生长因子-β和前列腺素 E 的合成。最后，在补充 BCAAs 的培养基中培养的 MSCs 可减少巨噬细胞产生的 IL-6 和肿瘤坏死因子-α。
BCAA 补充影响 MSCs 的某些免疫调节方面。
