{"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}
引用次数: 1
Abstract
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.