{"title":"委内瑞拉圆线虫衍生的血管内皮素通过抑制晚期糖基化终产物介导的信号传导受体改善哮喘发病机制","authors":"Daigo Tsubokawa , Masashi Satoh","doi":"10.1016/j.pupt.2022.102148","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>EF-hand Ca<sup>2+</sup><span>-binding proteins such as S100 protein family members are recognized by the receptor for advanced glycation end-products (RAGE) and are involved in the pathogenesis of asthma/allergic airway inflammation (AAI). Venestatin, an EF-hand Ca</span><sup>2+</sup><span>-binding protein, which is secreted by the parasitic helminth </span><span><em>Strongyloides</em><em> venezuelensis</em></span><span><span>, binds with RAGE and suppresses RAGE-mediated inflammatory responses after parasite invasion. In this study, we evaluated the effect of venestatin on pathogenesis in a </span>house dust mite (HDM) murine model of asthma/AAI.</span></p></div><div><h3>Methods</h3><p><span>Mice were intranasally treated with HDM, HDM with recombinant venestatin, or HDM with synthetic peptides, which were designed based on the EF-hand Ca</span><sup>2+</sup>-binding domain of venestatin. Pro-inflammatory responses in the lungs of mice were assessed.</p></div><div><h3>Results</h3><p><span>HDM treatment induced inflammatory </span>cell infiltration, phosphorylation of the mitogen-activated protein kinase and inhibitor κB, and production of the cytokines tumor necrosis factor-α and interleukin-5 in the lungs. Co-administration of recombinant venestatin with HDM suppressed these pro-inflammatory responses. Treatment with synthetic peptides reduced inflammatory cell infiltration in a RAGE-dependent manner.</p></div><div><h3>Conclusion</h3><p>The EF-hand domain of venestatin may have potential therapeutic benefits in asthma.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Strongyloides venezuelensis-derived venestatin ameliorates asthma pathogenesis by suppressing receptor for advanced glycation end-products-mediated signaling\",\"authors\":\"Daigo Tsubokawa , Masashi Satoh\",\"doi\":\"10.1016/j.pupt.2022.102148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>EF-hand Ca<sup>2+</sup><span>-binding proteins such as S100 protein family members are recognized by the receptor for advanced glycation end-products (RAGE) and are involved in the pathogenesis of asthma/allergic airway inflammation (AAI). Venestatin, an EF-hand Ca</span><sup>2+</sup><span>-binding protein, which is secreted by the parasitic helminth </span><span><em>Strongyloides</em><em> venezuelensis</em></span><span><span>, binds with RAGE and suppresses RAGE-mediated inflammatory responses after parasite invasion. In this study, we evaluated the effect of venestatin on pathogenesis in a </span>house dust mite (HDM) murine model of asthma/AAI.</span></p></div><div><h3>Methods</h3><p><span>Mice were intranasally treated with HDM, HDM with recombinant venestatin, or HDM with synthetic peptides, which were designed based on the EF-hand Ca</span><sup>2+</sup>-binding domain of venestatin. Pro-inflammatory responses in the lungs of mice were assessed.</p></div><div><h3>Results</h3><p><span>HDM treatment induced inflammatory </span>cell infiltration, phosphorylation of the mitogen-activated protein kinase and inhibitor κB, and production of the cytokines tumor necrosis factor-α and interleukin-5 in the lungs. Co-administration of recombinant venestatin with HDM suppressed these pro-inflammatory responses. Treatment with synthetic peptides reduced inflammatory cell infiltration in a RAGE-dependent manner.</p></div><div><h3>Conclusion</h3><p>The EF-hand domain of venestatin may have potential therapeutic benefits in asthma.</p></div>\",\"PeriodicalId\":20799,\"journal\":{\"name\":\"Pulmonary pharmacology & therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2022-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary pharmacology & therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1094553922000396\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553922000396","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 1
摘要
ef -hand Ca2+结合蛋白如S100蛋白家族成员被晚期糖基化终产物(RAGE)受体识别,并参与哮喘/过敏性气道炎症(AAI)的发病机制。Venestatin是一种EF-hand Ca2+结合蛋白,由寄生蠕虫委内瑞拉圆线虫分泌,与RAGE结合并抑制寄生虫入侵后RAGE介导的炎症反应。在这项研究中,我们评估了venestatin对哮喘/AAI的屋尘螨(HDM)小鼠模型发病机制的影响。方法采用基于vegf -hand Ca2+结合结构域设计的HDM、重组血管内皮素HDM和合成肽对smice进行鼻内处理。评估小鼠肺部的促炎反应。结果shdm诱导肺组织炎症细胞浸润,丝裂原活化蛋白激酶和抑制因子κB磷酸化,细胞因子肿瘤坏死因子-α和白细胞介素-5产生。重组血管内皮素与HDM联合使用可抑制这些促炎反应。用合成肽治疗以rage依赖的方式减少炎症细胞浸润。结论内皮素的EF-hand结构域对哮喘有潜在的治疗作用。
Strongyloides venezuelensis-derived venestatin ameliorates asthma pathogenesis by suppressing receptor for advanced glycation end-products-mediated signaling
Introduction
EF-hand Ca2+-binding proteins such as S100 protein family members are recognized by the receptor for advanced glycation end-products (RAGE) and are involved in the pathogenesis of asthma/allergic airway inflammation (AAI). Venestatin, an EF-hand Ca2+-binding protein, which is secreted by the parasitic helminth Strongyloides venezuelensis, binds with RAGE and suppresses RAGE-mediated inflammatory responses after parasite invasion. In this study, we evaluated the effect of venestatin on pathogenesis in a house dust mite (HDM) murine model of asthma/AAI.
Methods
Mice were intranasally treated with HDM, HDM with recombinant venestatin, or HDM with synthetic peptides, which were designed based on the EF-hand Ca2+-binding domain of venestatin. Pro-inflammatory responses in the lungs of mice were assessed.
Results
HDM treatment induced inflammatory cell infiltration, phosphorylation of the mitogen-activated protein kinase and inhibitor κB, and production of the cytokines tumor necrosis factor-α and interleukin-5 in the lungs. Co-administration of recombinant venestatin with HDM suppressed these pro-inflammatory responses. Treatment with synthetic peptides reduced inflammatory cell infiltration in a RAGE-dependent manner.
Conclusion
The EF-hand domain of venestatin may have potential therapeutic benefits in asthma.
期刊介绍:
Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews.
Research Areas Include:
• All major diseases of the lung
• Physiology
• Pathology
• Drug delivery
• Metabolism
• Pulmonary Toxicology.