Bang Mi-Ae, Seo Ji-Hye, Seo Joung-Wook, Jo Gyung Hyun, Jung Seoung Ki, Yu Ri, Park Dae-Hun, Park Sang-Joon
Food Industry Development Team, Jeonnam Biofood Technology Center, Naju, Korea.
Department of Oriental Medicine Materials, Dongshin University, Naju, Korea.
PLoS One. 2015 Feb 6;10(2):e0117524. doi: 10.1371/journal.pone.0117524. eCollection 2015.
According to the World Health Organization in 2013, 235 million people are afflicted with asthma. Asthma is a severe pulmonary disease that can be caused by the imbalance of T-helper (Th) type 1 (Th1) and type 2 (Th2) cells, and it is potentially fatal. In this study, we evaluated the anti-asthmatic effect of alginate oligosaccharide (AO), which was prepared from seaweed and converted by Bacillus subtilis KCTC 11782BP, in the mouse model of ovalbumin (OVA)-induced asthma. BALB/c mice were divided into the vehicle control (sensitized but not challenged), asthma induction, positive control (1 mg/kg dexamethasone), 50 mg/kg/day AO-treated, 200 mg/kg/day AO-treated, and 400 mg/kg/day AO-treated groups. The numbers or levels of inflammatory cells, eosinophils, and immunoglobulin (Ig) E were measured in bronchoalveolar lavage fluid (BALF), and asthma-related morphological and cytokine changes were analyzed in lung tissues. Our results show that AO dramatically reduced inflammatory cell numbers, eosinophil count, and IgE levels in BALF, and it dose-dependently inhibited asthmatic histopathological changes in the lung. In addition, AO dose-dependently suppressed the expression of CD3+ T-cell co-receptors, CD4+ Th cells, CD8+ cytotoxic T-cell-related factors, macrophages, and MHCII class. AO dose-dependently decreased the expression levels of Th1/2 cells-regulatory transcription factors such as GATA-3 which modulates Th2 cell proliferation and T-bet which does Th1 cell proliferation. The mRNA levels of all Th1/2-related cytokines, except IL-12α, were dose-dependently suppressed by AO treatment. In particular, the mRNA levels of IL-5, IL-6, and IL-13 were significantly inhibited by AO treatment. Our findings suggest that AO has the potential to be an anti-asthmatic drug candidate, due to its modulation of Th1/Th2 cytokines, which contribute to the pathogenesis of asthma.
根据世界卫生组织2013年的数据，有2.35亿人患有哮喘。哮喘是一种严重的肺部疾病，可能由1型辅助性T（Th1）细胞和2型辅助性T（Th2）细胞失衡引起，且有潜在致命风险。在本研究中，我们评估了由海藻制备并经枯草芽孢杆菌KCTC 11782BP转化得到的海藻酸寡糖（AO）在卵清蛋白（OVA）诱导的哮喘小鼠模型中的抗哮喘作用。将BALB/c小鼠分为溶剂对照组（致敏但未激发）、哮喘诱导组、阳性对照组（1 mg/kg地塞米松）、50 mg/kg/天AO处理组、200 mg/kg/天AO处理组和400 mg/kg/天AO处理组。检测支气管肺泡灌洗液（BALF）中炎症细胞、嗜酸性粒细胞和免疫球蛋白（Ig）E的数量或水平，并分析肺组织中与哮喘相关的形态学和细胞因子变化。我们的结果表明，AO显著降低了BALF中的炎症细胞数量以及嗜酸性粒细胞计数和IgE水平，并剂量依赖性地抑制了肺部哮喘相关的组织病理学变化。此外，AO剂量依赖性地抑制了CD3 + T细胞共受体、CD4 + Th细胞、CD8 + 细胞毒性T细胞相关因子、巨噬细胞和MHCII类分子的表达。AO剂量依赖性地降低了Th1/2细胞调节转录因子的表达水平，如调节Th2细胞增殖的GATA - 3和调节Th1细胞增殖的T - bet。除IL - 12α外，所有Th1/2相关细胞因子的mRNA水平均被AO处理剂量依赖性地抑制。特别是，IL - 5、IL - 6和IL - 13的mRNA水平被AO处理显著抑制。我们的研究结果表明，AO有潜力成为一种抗哮喘药物候选物，因为它能调节Th1/Th2细胞因子，而这些细胞因子在哮喘发病机制中起作用。
