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康普茶通过激活 Treg 和 Th2 细胞来改善实验性自身免疫性脑脊髓炎。

Kombucha ameliorates experimental autoimmune encephalomyelitis through activation of Treg and Th2 cells.

机构信息

Department of Pathology and Laboratory Medicine, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

Acta Neurol Belg. 2021 Dec;121(6):1685-1692. doi: 10.1007/s13760-020-01475-3. Epub 2020 Aug 18.

DOI:10.1007/s13760-020-01475-3
PMID:32812134
Abstract

Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS). Kombucha is produced by the fermentation of sugared tea with a symbiotic culture of bacteria and yeasts. This research was designed to reveal the therapeutic impact and the molecular and cellular processes determining the effect of kombucha on MS alleviation in an experimental autoimmune encephalomyelitis (EAE). The EAE was induced using myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in CFA and injected subcutaneously over two flank areas in C57BL/6 mice. In addition, pertussis toxin was injected intraperitoneally and repeated 48 h later. Treatment groups were received three different doses of kombucha (K1: low dose, K2: medium dose and K3: high dose) to obtain a maximum protection. Clinical scores and other criteria were followed daily for the 25 days. At the end of the course, T-helper-related cytokines (IFN-γ, IL-17, IL-4, and TGF-β) were measured through ELISA. Moreover, nitric oxide (NO) concentration in spinal cord tissue was detected. The severity of disease on the peak of disease in K1, K2, and K3 groups were 3.4 ± 0.18 and 2.6 ± 0.18 and 2 ± 0.14 respectively, compared to the CTRL group with 4.5 ± 0.19 (p < 0.001). Kombucha increased production of interleukin IL-4 (K1 = 95 ± 5, K2 = 110 ± 10, K3 = 115 ± 5 and CTRL = 65 ± 5; p < 0.05) and TGF-β (K1 = 1750 ± 80, K2 = 2050 ± 65, K3 = 2200 ± 75 and CTRL = 850 ± 85; p < 0.001) but concurrently resulted in a remarkable reduction in the production of IFN-γ (K1 = 950 ± 70, K2 = 890 ± 65, K3 = 850 ± 85 and CTRL = 3850 ± 115; p < 0.001) and IL-17 (K1 = 1250 ± 75, K2 = 1050 ± 90, K3 = 970 ± 80 and CTRL = 6450 ± 125; p < 0.001). Moreover, NO concentration in spinal cord tissue in the treatment groups was significantly less than the control group (K1: 35.42 ± 2.1, K2 = 31.21 ± 2.2, K3 = 28.24 ± 2.6 and CTRL = 45.25 ± 2.7; p < 0.05). These results supported that kombucha could reduce the severity of disease in an EAE model through motivating polarization of CD4 T cells by induction of IL-4 and TGF-β as well as inhibition of IFN-γ and IL-17.

摘要

多发性硬化症(MS)是中枢神经系统(CNS)最常见的炎症性疾病。康普茶是通过糖茶与细菌和酵母共生培养发酵制成的。本研究旨在揭示 Kombucha 对实验性自身免疫性脑脊髓炎(EAE)缓解的治疗作用及其决定其疗效的分子和细胞过程。通过将髓鞘少突胶质细胞糖蛋白(MOG)肽乳化在 CFA 中并在 C57BL/6 小鼠的两个侧腹区域皮下注射,诱导 EAE。此外,还通过腹腔内注射百日咳毒素,并在 48 小时后重复注射。治疗组接受三种不同剂量的 Kombucha(K1:低剂量,K2:中剂量和 K3:高剂量)以获得最大保护。在 25 天的时间里,每天都要对临床评分和其他标准进行跟踪。在疗程结束时,通过 ELISA 测量 T 辅助相关细胞因子(IFN-γ、IL-17、IL-4 和 TGF-β)。此外,还检测了脊髓组织中一氧化氮(NO)的浓度。与对照组(4.5±0.19,p<0.001)相比,K1、K2 和 K3 组在疾病高峰期的严重程度分别为 3.4±0.18、2.6±0.18 和 2.0±0.14。 Kombucha 增加了白细胞介素 IL-4 的产生(K1=95±5、K2=110±10、K3=115±5 和 CTRL=65±5;p<0.05)和 TGF-β(K1=1750±80、K2=2050±65、K3=2200±75 和 CTRL=850±85;p<0.001),但同时显著降低了 IFN-γ 的产生(K1=950±70、K2=890±65、K3=850±85 和 CTRL=3850±115;p<0.001)和 IL-17(K1=1250±75、K2=1050±90、K3=970±80 和 CTRL=6450±125;p<0.001)。此外,治疗组脊髓组织中 NO 浓度明显低于对照组(K1:35.42±2.1、K2=31.21±2.2、K3=28.24±2.6 和 CTRL=45.25±2.7;p<0.05)。这些结果表明,Kombucha 可以通过诱导 IL-4 和 TGF-β以及抑制 IFN-γ 和 IL-17 来极化 CD4 T 细胞,从而减轻 EAE 模型中的疾病严重程度。

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