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Production of functional human interleukin 37 using plants

机译:使用植物生产功能性人白细胞介素37

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Key messageWe demonstrate for the first time that a fully bioactive human IL-37, a newly discovered cytokine acting as a fundamental inhibitor of innate immunity, can be recombinantly produced in plant cells.AbstractInterleukin 37 (IL-37), a newly discovered member of the interleukin (IL)-1 family of cytokines, plays a pivotal role in limiting innate inflammation and suppressing acquired immune responses, thus holding high potential for treating a wide array of human inflammatory and autoimmune disorders. In this study, we have developed transgenic plants as a novel expression platform for production of human IL-37 (IL-37). Plant transformation vectors synthesizing various forms of the b isoform of IL-37, including an unprocessed full-length precursor form (proIL-37b), a mature form (matIL-37b) and an IL-37 fusion protein in which IL-37b was fused to soybean agglutinin (SBA-IL-37b), have been constructed and introduced into tobacco plants. The expression of all forms of IL-37b was driven by a strong constitutive 35S promoter. Transgenic tobacco plants were generated with each of these constructs. Depending on the form of IL-37b being produced, the expression level of proIL-37b reached approximately 1% of TSP, while matIL-37b expression was substantially lower (0.01% TSP). Fusion to SBA substantially increased the expression of matIL-37b, with the expression level of fusion protein accounting for 1% of TSP. Functional analysis using a cell-based in vitro assay showed that plant-made matIL-37b and proIL-37b are both biologically active, but plant-made matIL-37b exhibited significantly greater biological activity than proIL-37b. These results demonstrate that plants have great potential of being a green bioreactor for low-cost, large-scale production of biologically active IL-37.
机译:关键消息我们首次证明了一种完全生物活性人IL-37,一种新发现的细胞因子作用作为先天免疫的基本抑制剂,可以在植物细胞中重组产生.AbstractInterleukin 37(IL-37),新发现的成员白细胞介素(IL)-1家族细胞因子在限制先天炎症和抑制获得的免疫应答中起着枢轴作用,从而占据各种人炎症和自身免疫疾病的高潜力。在这项研究中,我们开发了转基因植物作为用于生产人IL-37(IL-37)的新型表达平台。植物转化载体合成IL-37的各种形式的B同系形式,包括未加工的全长前体形式(ProIL-37b),成熟形式(Matil-37b)和IL-37融合蛋白,其中IL-37b是其中已经构建并引入烟草植物中与大豆凝集素(SBA-IL-37B)融合。所有形式的IL-37B的表达由强型35s启动子驱动。用这些构建体产生转基因烟草植物。取决于产生的IL-37B的形式,ProIL-37b的表达水平达到TSP的约1%,而Matil-37b表达基本上(0.01%TSP)。融合对SBA显着增加了Matil-37b的表达,融合蛋白表达水平占TSP的1%。使用基于细胞的体外测定的功能性分析显示,植物制造的Matil-37b和Proil-37b既是生物活性的,而且植物制造的Matil-37b比ProIL-37B表现出明显更大的生物活性。这些结果表明,植物具有用于低成本,生物活性IL-37的低成本,大规模生产的绿生生物反应器的潜力很大。

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