腺相关病毒载体递送Pannexin-1模拟肽减轻过敏原致敏小鼠模型中的气道炎症。

IF 3.9 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Human gene therapy Pub Date : 2023-11-01 Epub Date: 2023-10-18 DOI:10.1089/hum.2023.078
Yung-An Huang, Jeng-Chang Chen, Pei-Chuan Chiang, Li-Chen Chen, Ming-Ling Kuo
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引用次数: 0

摘要

哮喘是一种全球性的慢性炎症性疾病。细胞外三磷酸腺苷作为一种危险信号对细胞应激、刺激或炎症作出反应。据报道,它和哮喘的致病性有关,哮喘患者肺部的致病性水平升高。Pannexin-1是有助于三磷酸腺苷从细胞内释放到细胞外的途径之一。本研究的目的是将pannexin-1肽拮抗剂10Panx1应用于卵清蛋白(OVA)诱导的哮喘小鼠模型的腺相关病毒(AAV)载体中。结果表明,该治疗能够降低支气管肺泡灌洗液中的三磷酸腺苷水平,并下调与哮喘发作症状相关的主要因素,即气道对乙酰甲胆碱的高反应性。组织学数据也对组织重塑和粘液沉积的减少给予了积极支持。其他哮喘相关特征,包括嗜酸性粒细胞炎症和OVA特异性辅助T细胞2型反应,也因治疗而减少。除了炎症指数外,还检测了效应细胞和调节性T细胞的比例,以调查其背后的潜在机制。该数据提供了肺GATA3+CD4T细胞中略微下调的模式。然而,在脾脏中观察到CD25+FoxP3+CD4T细胞群的上调。这些数据表明,10Panx1肽的外源性表达有可能减轻哮喘气道炎症,这种治疗作用可能来自10Panx1介导的T细胞活化或分化的破坏。总之,AAV载体介导的10Panx1表达可能是一种海军治疗选择。
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Adeno-Associated Viral Vector-Delivered Pannexin-1 Mimetic Peptide Alleviates Airway Inflammation in an Allergen-Sensitized Mouse Model.

Asthma is a chronic inflammatory disease around the world. Extracellular adenosine triphosphate works as a dangerous signal in responding to cellular stress, irritation, or inflammation. It has also been reported its association with the pathogenicity in asthma, with increased level in lungs of asthmatics. Pannexin-1 is one of the routes that contributes to the release of adenosine triphosphate form intracellular to extracellular. The aim of this study was to apply pannexin-1 peptide antagonist 10Panx1 into adeno-associated viral (AAV) vectors on ovalbumin (OVA)-induced asthmatic mouse model. The results demonstrated that this treatment was able to reduce the adenosine triphosphate level in bronchoalveolar lavage fluid and downregulate the major relevant to the symptom of asthma attack, airway hyperresponsiveness to methacholine. The histological data also gave a positive support with decreased tissue remodeling and mucus deposition. Other asthmatic related features, including eosinophilic inflammation and OVA-specific T helper type 2 responses, were also decreased by the treatment. Beyond the index of inflammation, the proportion of effector and regulatory T cells was examined to survey the potential mechanism behind. The data provided a slightly downregulated pattern in lung GATA3+ CD4 T cells. However, an upregulated population of CD25+FoxP3+ CD4 T cells was seen in spleens. These data suggested that exogeneous expression of 10Panx1 peptide was potential to alleviated asthmatic airway inflammation, and this therapeutic effect might be from 10Panx1-mediated disruption of T cell activation or differentiation. Collectively, AAV vector-mediated 10Panx1 expression could be a naval therapy option to develop.

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来源期刊
Human gene therapy
Human gene therapy 医学-生物工程与应用微生物
CiteScore
6.50
自引率
4.80%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.
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