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来源于人嗜酸性粒细胞阳离子蛋白的细胞穿透肽可减轻气道变应性炎症。

Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation.

机构信息

Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan.

Pediatrics Department, National Yang-Ming Medical University, Taipei, Taiwan.

出版信息

Sci Rep. 2017 Sep 27;7(1):12352. doi: 10.1038/s41598-017-12390-8.

DOI:10.1038/s41598-017-12390-8
PMID:28955044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5617860/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/7f7a336eb09e/41598_2017_12390_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/d7753b6f370c/41598_2017_12390_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4695c3a2b65f/41598_2017_12390_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/83e8da9f3ace/41598_2017_12390_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/3f1ff8388df3/41598_2017_12390_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4c7cb237cb29/41598_2017_12390_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4d027e227c5d/41598_2017_12390_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/ad6506187462/41598_2017_12390_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/e5d0772e3832/41598_2017_12390_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/7f7a336eb09e/41598_2017_12390_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/d7753b6f370c/41598_2017_12390_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4695c3a2b65f/41598_2017_12390_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/83e8da9f3ace/41598_2017_12390_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/3f1ff8388df3/41598_2017_12390_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4c7cb237cb29/41598_2017_12390_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/4d027e227c5d/41598_2017_12390_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/ad6506187462/41598_2017_12390_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/e5d0772e3832/41598_2017_12390_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005a/5617860/7f7a336eb09e/41598_2017_12390_Fig9_HTML.jpg

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