离子通道，即瞬时受体电位阳离子通道亚家族V成员1（TRPV1），在过敏性哮喘中的作用。
Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma.
作者信息
Baker Katie, Raemdonck Kristof, Dekkak Bilel, Snelgrove Robert J, Ford John, Shala Fisnik, Belvisi Maria G, Birrell Mark A
机构信息
Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. HernâniMonteiro, 4200-319, Porto, Portugal.
出版信息
Respir Res. 2016 Jun 2;17(1):67. doi: 10.1186/s12931-016-0384-x.
BACKGROUND
Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals.
METHODS
Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation.
RESULTS
CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes.
CONCLUSION
Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.
背景
哮喘患病率在全球范围内尤其是在儿童中有所上升；因此，需要开发新的安全有效的治疗方法，特别是针对重度/难治性哮喘患者。CD4(+) T细胞被认为在疾病发病机制和相关症状中起核心作用。最近，已证明瞬时受体电位香草酸亚型1（TRPV1）可调节CD4(+)细胞的激活和炎症特性。这些实验的目的是使用临床可用的TRPV1抑制剂（XEN-D0501）和基因改造（GM）动物，证明CD4(+) T细胞在哮喘模型中的重要性以及TRPV1的作用。
方法
用抗原（屋尘螨或卵清蛋白）致敏小鼠（野生型、CD4 (-/-)或TRPV1 (-/-)）和大鼠，随后用相同抗原进行局部激发。测量与过敏性哮喘样表型相关的关键特征：肺功能（气道高反应性[AHR]和迟发性哮喘反应[LAR]）、过敏状态（IgE水平）和气道炎症。
结果
CD4(+) T细胞在两个疾病模型系统中均起核心作用，所有哮喘样特征均减弱。使用基因改造小鼠或药理学抑制剂靶向TRPV1往往会降低IgE水平、气道炎症和肺功能变化。
结论
我们的数据表明TRPV1参与过敏性哮喘，因此我们认为该靶点值得进一步研究。
Zotero 插件