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Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis

机译:携带编码IL-10的pValac DNA表达载体的乳酸乳球菌可减轻小鼠实验性结肠炎模型的炎症

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Background Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract. Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study. We previously presented the development of an invasive strain of Lactococcus lactis ( L. lactis ) producing Fibronectin Binding Protein A (FnBPA) which was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac: il-10 ) and diminish inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of intestinal inflammation. As a new therapeutic strategy against IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains (the same invasive strain evaluated previously and the wild-type strain) carrying the therapeutic pValac: il-10 plasmid in the prevention of inflammation in a dextran sodium sulphate (DSS)-induced mouse model. Results Results obtained showed that not only delivery of the pValac: il-10 plasmid by the invasive strain L. lactis MG1363 FnBPA+, but also by the wild-type strain L. lactis MG1363, was effective at diminishing intestinal inflammation (lower inflammation scores and higher IL-10 levels in the intestinal tissues, accompanied by decrease of IL-6) in the DSS-induced IBD mouse model. Conclusions Administration of both L. lactis strains carrying the pValac: il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.
机译:背景技术炎症性肠病(IBD)是一种以胃肠道炎症为特征的肠道疾病。白介素10是参与肠道免疫系统的最重要的抗炎细胞因子之一,由于其在下调炎症级联反应中的作用,其IBD治疗的潜力正在研究中。我们以前曾提出过一种产乳胶球菌(L. lactis)侵袭性菌株的开发,该菌株可产生纤连蛋白结合蛋白A(FnBPA),该蛋白能够直接向宿主细胞传递编码小家鼠IL-10的真核DNA表达载体。 pValac:il-10)并减少三硝基苯磺酸(TNBS)诱导的小鼠肠道炎症模型的炎症。作为一种针对IBD的新治疗策略,这项工作的目的是评估两种乳酸乳球菌菌株(先前评估过的同一侵袭性菌株和野生型菌株)在其体内携带治疗性pValac:il-10质粒的治疗效果。在右旋糖酐硫酸钠(DSS)诱导的小鼠模型中预防炎症。结果获得的结果表明,不仅通过侵染性菌株乳酸乳球菌MG1363 FnBPA +传递pValac:il-10质粒,而且通过野生型菌株乳酸乳球菌MG1363传递都可有效减轻肠道炎症(降低炎症评分和在DSS诱导的IBD小鼠模型中,肠道组织中的IL-10水平升高,IL-6降低。结论在该实验性结肠炎的小鼠模型中,两种携带pValac:il-10质粒的乳酸乳球菌的施用均能有效减轻炎症,显示出它们对IBD的治疗干预的潜力。

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