Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma.
Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma.
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DOI：
10.1186/s12931-016-0384-x
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发表时间：
2016-06-02
影响因子：
5.8
通讯作者：
Birrell MA
中科院分区：
文献类型：
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作者：
Baker K;Raemdonck K;Dekkak B;Snelgrove RJ;Ford J;Shala F;Belvisi MG;Birrell MA
哮喘患病率在世界范围内增加，特别是在儿童中;因此需要开发安全有效的新疗法，特别是对于重度/难治性哮喘患者。CD 4 + T细胞被认为在疾病发病机制和相关症状中发挥核心作用。最近，TRPV 1已被证明可以调节CD 4+细胞的激活和炎症特性。这些实验的目的是证明CD 4 + T细胞的重要性和TRPV 1在哮喘模型中的作用，使用临床上现成的TRPV 1抑制剂（XEN-D 0501）和遗传修饰（GM）动物。小鼠（野生型、CD 4 −/−或TRPV 1 −/−）和大鼠用抗原（HDM或OVA）致敏，随后用相同抗原局部激发。测定与过敏性哮喘类型表型相关的关键特征：肺功能（气道高反应性[AHR]和晚期哮喘反应[LAR]）、过敏状态（IgE水平）和气道炎症。CD 4 + T细胞在两种疾病模型系统中均发挥核心作用，所有哮喘样特征均减弱。使用GM小鼠或药物抑制剂靶向TRPV 1倾向于降低IgE水平，气道炎症和肺功能变化。我们的数据表明TRPV 1参与过敏性哮喘，因此我们认为该靶点值得进一步研究。
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. 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. 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. Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.