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首页> 外文期刊>Journal of the American Society of Nephrology: JASN >In vitro and in vivo immunomodulatory effects of RDP1258, a novel synthetic peptide.
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In vitro and in vivo immunomodulatory effects of RDP1258, a novel synthetic peptide.

机译：RDP1258（一种新型合成肽）的体外和体内免疫调节作用。

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摘要

Peptides derived from certain regions of human class I MHC molecules are known to have immunomodulatory effects. In particular, amino acid residues 75-84 of the HLA-B7 and HLA-B2702 molecules have demonstrated allele nonspecific immunosuppression in several animal transplant models. There is evidence that these effects are mediated by binding to intracellular heat shock proteins, including heme oxygenase-1. A new derivative of these peptides, RDP1258, was developed using a novel computer-assisted rational design technique. In vitro, RDP1258 peptide inhibited rat heme oxygenase activity in a dose-dependent manner. Similar to observations made with other in vitro heme oxygenase inhibitors, in vivo administration of RDP1258 peptide to naive rats resulted in upregulation of splenic heme oxygenase activity. The effects of the peptide on alloimmune responses were then tested. Addition of RDP1258 to rat and human mixed leukocyte reactions inhibited proliferation in a dose-dependent manner. In a rat renal transplantation model, peptide therapy combined with a sub-therapeutic dose of cyclosporin A significantly prolonged allograft survival. These data provide further evidence that modulation of the heat shock protein heme oxygenase by rationally designed peptides affects immune effector functions and may allow the development of novel immunomodulatory strategies in organ transplantation.
机译：已知衍生自人类I类MHC分子某些区域的肽具有免疫调节作用。特别地，在几种动物移植模型中，HLA-B7和HLA-B2702分子的氨基酸残基75-84已显示出等位基因非特异性免疫抑制。有证据表明，这些作用是通过与细胞内热休克蛋白（包括血红素加氧酶-1）结合而介导的。使用新型的计算机辅助合理设计技术开发了这些肽的新衍生物RDP1258。在体外，RDP1258肽以剂量依赖性方式抑制大鼠血红素加氧酶活性。与其他体外血红素加氧酶抑制剂的观察结果相似，向幼稚大鼠体内施用RDP1258肽导致脾脏血红素加氧酶活性上调。然后测试了肽对同种免疫应答的影响。 RDP1258添加到大鼠和人类混合白细胞反应以剂量依赖的方式抑制增殖。在大鼠肾移植模型中，肽疗法与亚治疗剂量的环孢菌素A联合可显着延长同种异体移植的存活时间。这些数据提供了进一步的证据，表明合理设计的肽对热休克蛋白血红素加氧酶的调节会影响免疫效应器功能，并可能允许开发器官移植中的新型免疫调节策略。

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