Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model
Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model
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DOI：
10.5483/bmbrep.2013.46.2.272
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发表时间：
2013-02-28
期刊：
影响因子：
3.8
通讯作者：
Choi, Soo Young
中科院分区：
文献类型：
--
作者：
Kim, Dae Won;Lee, Sung Ho;Choi, Soo Young
FK 506结合蛋白12（FK 506 BP）属于亲免疫蛋白家族，参与多种生物学过程。然而，FK 506 BP在角膜疾病中的功能尚不清楚。在这项研究中，我们研究了在肉毒杆菌毒素A（BTX-A）诱导的小鼠模型中，使用细胞渗透性PEP-1-FK 506 BP蛋白对干眼病的保护作用。PEP-1-FK 506 BP以时间和剂量依赖性方式有效地转导到人角膜上皮细胞中，并在细胞中保持稳定48 h。此外，我们证明，局部应用PEP-1-FK 506 BP转导到小鼠角膜和结膜的免疫组织化学。此外，将PEP-1-FK 506 BP局部应用于BTX-A诱导的小鼠模型显著抑制角膜和结膜上皮中促炎细胞因子如白介素-1 β（IL-1 β）、肿瘤坏死因子-α（TNF-α）和巨噬细胞抑制因子（MIF）的表达水平。提示PEP-1-FK 506 BP是一种潜在的治疗干眼病的药物。[BMB报告2013; 46（2）：124-129]
FK506 binding protein 12 (FK506BP) belongs to a family of immunophilins, and is involved in multiple biological processes. However, the function of FK506BP in corneal disease remains unclear. In this study, we examined the protective effects on dry eye disease in a Botulinum toxin A (BTX-A) induced mouse model, using a cell-permeable PEP-1-FK506BP protein. PEP-1-FK506BP efficiently transduced into human corneal epithelial cells in a time- and dose-dependent manner, and remained stable in the cells for 48 h. In addition, we demonstrated that topical application of PEP-1-FK506BP was transduced into mouse cornea and conjunctiva by immunohistochemistry. Furthermore, topical application of PEP-1-FK506BP to BTX-A-induced mouse model markedly inhibited expression levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and macrophage inhibitory factor (MIF) in corneal and conjunctival epithelium. These results suggest PEP-1-FK506BP as a potential therapeutic agent for dry eye diseases. [BMB Reports 2013; 46(2): 124-129]