Research Article

前胸腺素及其C端免疫反应性十肽无急性毒性证据:计算机模拟、体外和体内研究初探

卷 29, 期 42, 2022

发表于: 14 January, 2022

页: [6463 - 6478] 页: 16

弟呕挨: 10.2174/0929867328666211117093401

价格: $65

摘要

背景:α-胸腺素家族成员的免疫刺激特性一直被研究。其中,危险相关分子模式(DAMPs)原胸腺素(proTα)及其C末端十肽proTα(100-109)已被证明在体外发挥免疫调节剂的作用,因为它们能够促进T辅助性T型1(Th1)反应。最近,我们在体内验证了这些发现,表明proTα和proTα(100-109)都增强了抗肿瘤T细胞介导的应答。 方法:鉴于proTα和proTα(100-109)在人类中的最终使用,我们研究了它们在计算机,体外人白细胞和癌细胞系以及体内免疫功能小鼠中的安全性,与proTα衍生物胸腺素α1(Τα1)相比,proTα衍生物胸腺素α1(Τα1)是一种28聚体肽,在临床试验中因其安全性而被广泛研究。 结果:通过计算工具进行 计算机预测显示,所有三个肽序列都可能是无毒的或不诱导过敏区域。 在体外,前Tα、proTα(100-109)和Tα1不影响人癌细胞系和健康供体来源白细胞的活力,不促进细胞凋亡或改变细胞周期分布。此外,以相当于人类Tα1建议剂量方案的剂量注射proTα,proTα(100-109)和Tα1的小鼠没有显示出急性毒性的迹象,而proTα和proTα(100-109)增加了其外周血中促炎和Th1-型细胞因子的水平。 结论:我们的初步发现表明,即使在高浓度下,proTα和proTα(100-109)在体外和体内急性毒性模型中也是无毒的;此外,我们发现这两种肽在体内保持其免疫调节特性 ,最终可以考虑用于人类的治疗。

关键词: 潮湿,前胸腺素α,体内毒性,免疫调节,胸腺肽,胸腺素α1。

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