含对硝基苯丙氨酸的B淋巴细胞刺激因子疫苗对狼疮肾炎模型小鼠的保护作用

发布时间：2018-02-02 00:25

本文关键词： B淋巴细胞刺激因子对硝基苯丙氨酸免疫原性 cGVHD　出处：《中国药科大学学报》2017年04期 　论文类型：期刊论文

【摘要】：考察含对硝基苯丙氨酸的B淋巴细胞刺激因子(BAFF)治疗BAFF过表达的自身免疫性疾病的效果。利用本研究前期构建的工程菌,表达纯化了B淋巴细胞刺激因子的可溶型突变体(sm BAFF)以及在其65位定点引入了对硝基苯丙氨酸的改构体(pNO_2Phe~(65)sm BAFF)。通过考察pNO_2Phe~(65)sm BAFF体外促小鼠淋巴细胞增殖活性、免疫原性以及所诱导的抗血清对天然BAFF活性的抑制作用,评价了其用于治疗BAFF过表达的自身免疫性疾病的可行性;同时采用了cGVHD(graft-versus-host disease)诱导的狼疮肾炎小鼠模型评价了pNO_2Phe~(65)sm BAFF的药理活性。结果表明:定点引入了对硝基苯丙氨酸的pNO_2Phe~(65)sm BAFF不具有促进小鼠淋巴细胞增殖的能力;由于对硝基苯丙氨酸的引入显著增强了蛋白的免疫原性,诱导机体产生了可以抑制天然BAFF活性的交叉抗体;在cGVHD诱导的狼疮肾炎小鼠模型中,pNO_2Phe~(65)sm BAFF可显著减轻疾病症状。定点引入了对硝基苯丙氨酸的pNO_2Phe~(65)sm BAFF可以作为治疗BAFF过表达的自身免疫性疾病的候选分子。
[Abstract]:To investigate the efficacy of B lymphocyte stimulating factor (BAFF) containing p-nitrophenylalanine in the treatment of autoimmune diseases with overexpression of BAFF. The soluble mutant of B lymphocyte stimulating factor, Sm BAFF, was expressed and purified, and the p-nitrophenylalanine (p-nitrophenylalanine) was introduced into the mutagenesis of p-nitrophenylalanine at the 65-site. The proliferation activity of murine lymphocytes induced by pNO_2Phe~(65)sm BAFF was investigated in vitro. The immunogenicity and the inhibitory effect of the induced antiserum on the activity of natural BAFF were evaluated. The feasibility of its application in the treatment of autoimmune diseases with overexpression of BAFF was evaluated. The mice model of lupus nephritis induced by cGVHD(graft-versus-host disease was also used to evaluate pNO2Pheimian 65). The pharmacological activity of SM BAFF. The results showed that pNO_2Phe~(65)sm BAFF, which was introduced with p-nitrophenylalanine, had no ability to promote lymphocyte proliferation in mice. The introduction of p-nitrophenylalanine significantly enhanced the immunogenicity of the protein and induced the production of cross-antibodies that could inhibit the activity of natural BAFF. In cGVHD induced lupus nephritis mouse model. PNO_2Phe~(65)sm BAFF significantly alleviated the symptoms of the disease. The pNO2Phehe of p-nitrophenylalanine was introduced at targeted sites. SM BAFF can be used as a candidate for the treatment of BAFF overexpression in autoimmune diseases.
【作者单位】：中国药科大学江苏省生物药物成药性研究重点实验室生命科学与技术学院;
【基金】：国家自然科学基金资助项目(No.81273426,No.81673343)~~
【分类号】：R-332;R593.242
【正文快照】： B淋巴细胞刺激因子(B cell activating factor术[16],该技术可以模拟天然蛋白质的合成过程,直belonging to the TNF family,BAFF)是肿瘤坏死因子接表达出含非天然氨基酸的蛋白质,有助于产生治家族第13位成员,含有285个氨基酸,属于Ⅱ型跨疗性抗体。研究表明,将含有p NO2Phe的小

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