天然存在的 3RS、7R、11R-植烷酸可抑制体外 T 细胞产生干扰素-γ。
Naturally occurring 3RS, 7R, 11R-phytanic acid suppresses in vitro T-cell production of interferon-gamma.
机构信息
Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
Department of Applied Chemistry, Faculty of Engineering, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
出版信息
Lipids Health Dis. 2018 Jun 23;17(1):147. doi: 10.1186/s12944-018-0793-6.
BACKGROUND
Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study also investigated the effects of 3RS, 7R, 11R-PA on NF-κB activity in order to address the mechanism of its immunomodulatory effects.
METHODS
Mouse splenocytes and purified T-cells were stimulated with T-cell mitogens and incubated with 3RS, 7R, 11R-PA, followed by evaluation of IFN-γ production. The effect of 3RS, 7R, 11R-PA on NF-κB activity was also investigated using an A549 cell line with stable expression of an NF-κB-dependent luciferase reporter gene.
RESULTS
3RS, 7R, 11R-PA significantly reduced in vitro IFN-γ production at both the protein and mRNA levels, and was accompanied by decreased expression of T-bet, a key regulator of Th1 cell differentiation. The results indicated that NF-κB-mediated transcriptional activity was significantly decreased by 3RS, 7R, 11R-PA and that GW6471, an antagonist of peroxisome proliferator activated receptor α (PPARα), abrogated the inhibitory effect of 3RS, 7R, 11R-PA on NF-κB activity.
CONCLUSIONS
The present study suggests that 3RS, 7R, 11R-PA is a functional and bioactive fatty acid, and has a potentially beneficial effect for amelioration of T-cell mediated autoimmune diseases. This study also indicates that interference in the NF-κB pathway via PPARα activation is a potential mechanism of the immunomodulatory effects of 3RS, 7R, 11R-PA.
背景
在植烷酸（PA）的八个立体异构体中，3RS、7R、11R-异构体是天然存在的，存在于食物和人体中。PA 被认为对免疫系统有潜在的健康益处。然而，由于以前的研究使用的是商业上可获得的 PA，其异构体构型未知，因此这些影响是否是由 3RS、7R、11R-PA 异构体引起的仍不确定。在这项研究中，我们合成了 3RS、7R、11R-PA 的制剂，并研究了其体外免疫调节作用，特别是与各种自身免疫性疾病相关的干扰素（IFN）-γ的 T 细胞产生。本研究还研究了 3RS、7R、11R-PA 对 NF-κB 活性的影响，以探讨其免疫调节作用的机制。
方法
用 T 细胞有丝分裂原刺激小鼠脾细胞和纯化的 T 细胞，并用 3RS、7R、11R-PA 孵育，然后评估 IFN-γ的产生。还使用稳定表达 NF-κB 依赖性荧光素酶报告基因的 A549 细胞系研究了 3RS、7R、11R-PA 对 NF-κB 活性的影响。
结果
3RS、7R、11R-PA 显著降低了体外 IFN-γ的蛋白和 mRNA 水平，同时 T 细胞分化的关键调节因子 T-bet 的表达也降低了。结果表明，3RS、7R、11R-PA 显著降低了 NF-κB 介导的转录活性，而 PPARα 拮抗剂 GW6471 则消除了 3RS、7R、11R-PA 对 NF-κB 活性的抑制作用。
结论
本研究表明 3RS、7R、11R-PA 是一种功能性和生物活性脂肪酸，对改善 T 细胞介导的自身免疫性疾病可能有有益作用。本研究还表明，通过激活 PPARα 干扰 NF-κB 途径是 3RS、7R、11R-PA 免疫调节作用的潜在机制。
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