Effects of TRPV4 channel blocker on airway inflammation and airway defense reflexes in experimentally induced model of allergic asthma

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology Pub Date : 2023-10-01 DOI:10.1016/j.resp.2023.104123

Jozef Mažerik , Eduard Gondáš , Lukáš Smieško , Soňa Fraňová , Martina Šutovská

{"title":"Effects of TRPV4 channel blocker on airway inflammation and airway defense reflexes in experimentally induced model of allergic asthma","authors":"Jozef Mažerik , Eduard Gondáš , Lukáš Smieško , Soňa Fraňová , Martina Šutovská","doi":"10.1016/j.resp.2023.104123","DOIUrl":null,"url":null,"abstract":"<div>The transient receptor potential (TRP) channels regulate physiological and pathological processes. Changes in their activity and sensitivity may be involved in the pathophysiology of asthma. The present study investigates the effect of an inhaled TRPV4 channel blocker HC-067047 in an experimental guinea pig model of ovalbumin-induced allergic asthma. We monitored the effect of 50 nM, 100 nM, and 150 nM HC-067047 concentrations on airway defense reflexes in vivo and tracheal smooth muscle contractility in vitro. The anti-inflammatory action of HC-067047 was investigated by analysis of chronic inflammation markers from lung homogenates. The results suggest that HC-067047 can suppress airway defense reflexes in vivo and acetylcholine-induced contractility in vitro. Immunological analysis revealed that TRPV4 channel blockade leads to a decrease in the levels of inflammatory cytokines. An effect on airway defence reflexes and airway inflammation was observed using tested concentrations (50 mM, 100 mM, 150 mM) of HC-067047. The effects of HC-067047 on both airway defense reflexes and inflammation underline the role of TRPV4 channels in asthma and uncover therapeutic targets for developing innovative drugs in asthma therapy.</div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Physiology & Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1569904823001118","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The transient receptor potential (TRP) channels regulate physiological and pathological processes. Changes in their activity and sensitivity may be involved in the pathophysiology of asthma. The present study investigates the effect of an inhaled TRPV4 channel blocker HC-067047 in an experimental guinea pig model of ovalbumin-induced allergic asthma. We monitored the effect of 50 nM, 100 nM, and 150 nM HC-067047 concentrations on airway defense reflexes in vivo and tracheal smooth muscle contractility in vitro. The anti-inflammatory action of HC-067047 was investigated by analysis of chronic inflammation markers from lung homogenates. The results suggest that HC-067047 can suppress airway defense reflexes in vivo and acetylcholine-induced contractility in vitro. Immunological analysis revealed that TRPV4 channel blockade leads to a decrease in the levels of inflammatory cytokines. An effect on airway defence reflexes and airway inflammation was observed using tested concentrations (50 mM, 100 mM, 150 mM) of HC-067047. The effects of HC-067047 on both airway defense reflexes and inflammation underline the role of TRPV4 channels in asthma and uncover therapeutic targets for developing innovative drugs in asthma therapy.

查看原文本刊更多论文

TRPV4通道阻滞剂对实验性过敏性哮喘模型气道炎症和气道防御反射的影响

瞬时受体电位（TRP）通道调节生理和病理过程。其活性和敏感性的变化可能与哮喘的病理生理学有关。本研究调查了吸入TRPV4通道阻断剂HC-067047在卵清蛋白诱导的过敏性哮喘实验豚鼠模型中的作用。我们监测了50nM、100nM和150nM HC-067047浓度对体内气道防御反射和体外气管平滑肌收缩性的影响。通过分析来自肺匀浆的慢性炎症标志物来研究HC-067047的抗炎作用。结果表明，HC-067047在体内可抑制气道防御反射，在体外可抑制乙酰胆碱诱导的收缩性。免疫学分析显示，TRPV4通道阻断导致炎性细胞因子水平下降。使用测试浓度（50mM、100mM、150mM）的HC-067047观察到对气道防御反射和气道炎症的影响。HC-067047对气道防御反射和炎症的影响强调了TRPV4通道在哮喘中的作用，并揭示了开发哮喘治疗创新药物的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Respiratory Physiology & Neurobiology 医学-呼吸系统

CiteScore

4.80

自引率

8.70%

发文量

104

审稿时长

54 days

期刊介绍： Respiratory Physiology & Neurobiology (RESPNB) publishes original articles and invited reviews concerning physiology and pathophysiology of respiration in its broadest sense. Although a special focus is on topics in neurobiology, high quality papers in respiratory molecular and cellular biology are also welcome, as are high-quality papers in traditional areas, such as: -Mechanics of breathing- Gas exchange and acid-base balance- Respiration at rest and exercise- Respiration in unusual conditions, like high or low pressure or changes of temperature, low ambient oxygen- Embryonic and adult respiration- Comparative respiratory physiology. Papers on clinical aspects, original methods, as well as theoretical papers are also considered as long as they foster the understanding of respiratory physiology and pathophysiology.