Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan.
Pediatrics Department, National Yang-Ming Medical University, Taipei, Taiwan.
Sci Rep. 2017 Sep 27;7(1):12352. doi: 10.1038/s41598-017-12390-8.
Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.
细胞穿透肽来源于人嗜酸性粒细胞阳离子蛋白(CPPecp),是一种 10 个氨基酸组成的肽,包含人嗜酸性粒细胞阳离子蛋白(ECP)的核心肝素硫酸盐(HS)结合基序。它能与气道上皮细胞结合并穿透细胞,而没有细胞毒性作用。在这里,我们研究了 CPPecp 在 BEAS-2B 细胞系和螨诱导的 BALB/c 小鼠气道过敏性炎症中的气道保护作用。在 BEAS-2B 细胞中,CPPecp 降低 ECP 诱导的嗜酸性粒细胞趋化因子 mRNA 表达。CPPecp 还降低 ECP 和 IL-4 诱导的嗜酸性粒细胞趋化因子分泌和 p-STAT6 激活。体内研究表明 CPPecp 降低了螨诱导的气道炎症,表现在支气管肺泡灌洗液中嗜酸性粒细胞和中性粒细胞计数、支气管周围和肺泡病理学评分、肺蛋白提取物中细胞因子的产生,包括白细胞介素(IL)-5、IL-13、IL-17A/F、嗜酸性粒细胞趋化因子;以及乙酰甲胆碱刺激引起的呼吸暂停增强。CPPecp 处理组的血清螨特异性 IgE 水平也较低。在这项研究中,我们已经证明了 CPPecp 的体外和体内抗哮喘作用。