Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Int Immunopharmacol. 2019 Mar;68:164-170. doi: 10.1016/j.intimp.2018.12.063. Epub 2019 Jan 9.
Mesenchymal stem cells (MSCs) have broad immunomodulatory activities. These cells are a stable source of cytokine production such as interleukin-6 (IL6), monocyte chemoattractant protein-1 (MCP-1/CCL2) and vascular endothelial growth factor (VEGF). Fatty acid elevation in chronic metabolic diseases alters the microenvironment of MSCs and thereby, might affect their survival and cytokine production. In the present study, we investigated the effects of palmitate, the most abundant saturated free fatty acid (FFA) in plasma, and astaxanthin, a potent antioxidant, on cell viability and apoptosis in human bone marrow-driven mesenchymal stem cells. We also elucidated how palmitate and astaxanthin influence the inflammation in MSCs. Human mesenchymal stem cells were collected from an aspirate of the femurs and tibias marrow compartment. The effect of palmitate on cell viability, caspase activity and pro-inflammatory cytokines expression and secretion were evaluated. In addition, activation of the MAP kinases and NF-kB signaling pathways were investigated. The results showed that astaxanthin protected MSCs from palmitate-induced cell death. We found that palmitate significantly enhanced IL-6, VEGF and MCP-1 expression, and secretion in MSC cells. Increased cytokine expression was parallel to the enhanced phosphorylation of P38, ERK and IKKα-IKKβ. In addition, pretreatment with JNK, ERK, P38, and NF-kB inhibitors could correspondingly attenuate palmitate-induced expression of VEGF, IL-6, and MCP-1. Our results demonstrated that fatty acid exposure causes inflammatory responses in MSCs that can be alleviated favorably by astaxanthin treatment.
间充质干细胞（MSCs）具有广泛的免疫调节活性。这些细胞是细胞因子产生的稳定来源，例如白细胞介素-6（IL6）、单核细胞趋化蛋白-1（MCP-1/CCL2）和血管内皮生长因子（VEGF）。慢性代谢疾病中脂肪酸的升高改变了间充质干细胞的微环境，从而可能影响它们的存活和细胞因子的产生。在本研究中，我们研究了棕榈酸（血浆中最丰富的饱和游离脂肪酸（FFA））和虾青素（一种有效的抗氧化剂）对人骨髓来源的间充质干细胞活力和细胞凋亡的影响。我们还阐明了棕榈酸和虾青素如何影响间充质干细胞中的炎症。人骨髓间充质干细胞从股骨和胫骨骨髓腔的抽吸物中收集。评估了棕榈酸对细胞活力、半胱天冬酶活性以及促炎细胞因子表达和分泌的影响。此外，还研究了 MAP 激酶和 NF-kB 信号通路的激活。结果表明，虾青素可保护 MSCs 免受棕榈酸诱导的细胞死亡。我们发现棕榈酸可显著增强 MSC 细胞中 IL-6、VEGF 和 MCP-1 的表达和分泌。细胞因子表达的增加与 P38、ERK 和 IKKα-IKKβ 的磷酸化增强平行。此外，用 JNK、ERK、P38 和 NF-kB 抑制剂预处理可以相应地减弱棕榈酸诱导的 VEGF、IL-6 和 MCP-1 的表达。我们的结果表明，脂肪酸暴露会引起 MSCs 中的炎症反应，虾青素处理可以有利地减轻这种反应。
