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Effect of recombinant serine protease from newborn larval stage of Trichinella spiralis on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis in mice.
Acta Tropica ( IF 2.7 ) Pub Date : 2020-06-17 , DOI: 10.1016/j.actatropica.2020.105553
Zheng Qu 1 , Xuemin Jin 1 , Yang Wang 1 , Yaming Yang 2 , Yang Li 1 , Xue Bai 1 , Yong Yang 1 , Ning Xu 1 , Xuelin Wang 1 , Mingyuan Liu 3
Affiliation  

Inflammatory bowel disease (IBD) is a complex immune-mediated disease of gastrointestinal tract that is mainly driven by Th1/Th17 immune response. “Helminth therapy” has emerged, and helminth-derived immunoregulatory molecules are being used as safe and new therapeutic antigens for IBD. Recombinant serine protease (SP) from newborn Trichinella spiralis (T. spiralis) larvae (NBL) was expressed and purified. BALB/c mice were immunized with NBL-SP at 100 µg three times at an interval of 5 days. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration. The disease activity index (DAI) and macroscopic and microscopic scores of the colon were assessed to identify the effect of NBL-SP on experimental colitis. Cytokine production in the serum was analysed by meso scale discovery (MSD). Cytokine production in the colon was detected by ELISA. CD4+ T cell differentiation was measured by flow cytometry. NBL-SP alleviated TNBS-induced colitis in mice. The DAI, macroscopic and microscopic scores and colon length all showed a positive intervention effect of NBL-SP on experimental colitis. NBL-SP can weaken the increase in IFN-γ, TNF-α and IL-17 production as well as CD4+ IFN-γ+ T cell and CD4+IL-17+ T cell populations induced by colitis. Furthermore, the levels of Th2-related cytokines (IL-4, IL-5) and regulatory cytokines (IL-10, TGF-β) were elevated meanwhile the ratio of regulatory T cells (Tregs) and CD4+ IL-4 + T cells were increased by NBL-SP. NBL-SP of T. spiralis had a potential protective effect against IBD. NBL-SP skewed the Th1 and Th17-mediated response towards the Th2 and Treg response.



中文翻译:

旋毛虫新生幼虫期重组丝氨酸蛋白酶对2,4,6-三硝基苯磺酸诱导的小鼠实验性结肠炎的影响。

炎症性肠病(IBD)是一种复杂的免疫介导的胃肠道疾病,主要由Th1 / Th17免疫反应驱动。“蠕虫疗法”已经出现,并且蠕虫衍生的免疫调节分子被用作IBD的安全和新型治疗抗原。新生旋毛虫T. spiralis)的重组丝氨酸蛋白酶(SP)表达并纯化幼虫(NBL)。以100 µg NBL-SP免疫BALB / c小鼠,每5天间隔3次。实验性结肠炎是由2,4,6-三硝基苯磺酸(TNBS)给药引起的。评估疾病活动指数(DAI)以及结肠的宏观和微观得分,以鉴定NBL-SP对实验性结肠炎的影响。通过细观规模发现(MSD)分析血清中细胞因子的产生。通过ELISA检测结肠中细胞因子的产生。CD4 + T细胞分化通过流式细胞术测量。NBL-SP减轻了TNBS诱发的小鼠结肠炎。DAI,宏观和微观得分以及结肠长度均显示NBL-SP对实验性结肠炎具有积极的干预作用。NBL-SP可减弱由结肠炎引起的IFN-γ,TNF-α和IL-17以及CD4 + IFN-γ + T细胞和CD4 + IL-17 + T细胞群的增加。此外,Th2相关细胞因子(IL-4,IL-5)和调节性细胞因子(IL-10,TGF-β)的水平升高,同时调节性T细胞(Tregs)和CD4 + IL-4  +  T的比例升高NBL-SP增加了细胞的数量。的NBL-SP旋毛虫对IBD具有潜在的保护作用。NBL-SP使Th1和Th17介导的反应偏向Th2和Treg反应。

更新日期:2020-06-27
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