本文關(guān)鍵詞： B淋巴細(xì)胞刺激因子 對(duì)硝基苯丙氨酸 免疫原性 cGVHD　出處：《中國(guó)藥科大學(xué)學(xué)報(bào)》2017年04期 　論文類(lèi)型：期刊論文

【摘要】：考察含對(duì)硝基苯丙氨酸的B淋巴細(xì)胞刺激因子(BAFF)治療BAFF過(guò)表達(dá)的自身免疫性疾病的效果。利用本研究前期構(gòu)建的工程菌,表達(dá)純化了B淋巴細(xì)胞刺激因子的可溶型突變體(sm BAFF)以及在其65位定點(diǎn)引入了對(duì)硝基苯丙氨酸的改構(gòu)體(pNO_2Phe~(65)sm BAFF)。通過(guò)考察pNO_2Phe~(65)sm BAFF體外促小鼠淋巴細(xì)胞增殖活性、免疫原性以及所誘導(dǎo)的抗血清對(duì)天然BAFF活性的抑制作用,評(píng)價(jià)了其用于治療BAFF過(guò)表達(dá)的自身免疫性疾病的可行性;同時(shí)采用了cGVHD(graft-versus-host disease)誘導(dǎo)的狼瘡腎炎小鼠模型評(píng)價(jià)了pNO_2Phe~(65)sm BAFF的藥理活性。結(jié)果表明:定點(diǎn)引入了對(duì)硝基苯丙氨酸的pNO_2Phe~(65)sm BAFF不具有促進(jìn)小鼠淋巴細(xì)胞增殖的能力;由于對(duì)硝基苯丙氨酸的引入顯著增強(qiáng)了蛋白的免疫原性,誘導(dǎo)機(jī)體產(chǎn)生了可以抑制天然BAFF活性的交叉抗體;在cGVHD誘導(dǎo)的狼瘡腎炎小鼠模型中,pNO_2Phe~(65)sm BAFF可顯著減輕疾病癥狀。定點(diǎn)引入了對(duì)硝基苯丙氨酸的pNO_2Phe~(65)sm BAFF可以作為治療BAFF過(guò)表達(dá)的自身免疫性疾病的候選分子。
[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.
【作者單位】： 中國(guó)藥科大學(xué)江蘇省生物藥物成藥性研究重點(diǎn)實(shí)驗(yàn)室生命科學(xué)與技術(shù)學(xué)院;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81273426,No.81673343)~~
【分類(lèi)號(hào)】：R-332;R593.242
【正文快照】： B淋巴細(xì)胞刺激因子(B cell activating factor術(shù)[16],該技術(shù)可以模擬天然蛋白質(zhì)的合成過(guò)程,直belonging to the TNF family,BAFF)是腫瘤壞死因子接表達(dá)出含非天然氨基酸的蛋白質(zhì),有助于產(chǎn)生治家族第13位成員,含有285個(gè)氨基酸,屬于Ⅱ型跨療性抗體。研究表明,將含有p NO2Phe的小

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