IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma.
IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma.
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DOI：
10.1016/j.jaci.2013.04.012
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发表时间：
2013-09
影响因子：
14.2
通讯作者：
Lloyd, Clare M.
中科院分区：
文献类型：
--
作者：
Saglani, Sejal;Lui, Stephen;Ullmann, Nicola;Campbell, Gaynor A.;Sherburn, Rebekah T.;Mathie, Sara A.;Denney, Laura;Bossley, Cara J.;Oates, Timothy;Walker, Simone A.;Bush, Andrew;Lloyd, Clare M.
重症难治性哮喘(STRA)患儿的症状和病理与Th2细胞因子无关。白细胞介素33(IL-33)可诱导气道高反应性(AHR)，但其在气道重塑和激素抵抗中的作用尚不清楚。目的：探讨IL-33与儿科气道重塑的关系。对吸入室内粉尘(HDM)的新生小鼠的IL-33进行了定量检测，并观察了阻断IL-13对其重塑和IL-33的影响。对缺乏IL-33受体的新生st2−/−小鼠进行了HDM诱导的变态反应性呼吸道疾病的评估，以及IL-33给药后胶原蛋白的产生。探讨激素治疗对新生儿AAD患者IL-33水平的影响。定量检测与重构相关的IL-33在STRA患儿支气管内膜活检组织中的表达，定量检测经IL-33和布地奈德刺激的儿童呼吸道成纤维细胞的胶原生成。在新生小鼠AAD建立后阻断IL-13不会减少重构或IL-33水平；AHR仅部分减少。IL-33促进儿童哮喘成纤维细胞的胶原合成，并在小鼠鼻内给药后促进。在患有STRA的儿童的支气管内活检组织中，IL-33的细胞表达增加，但与网状基底膜厚度增加无关，而在接触HDM的ST2−/−小鼠中则没有重塑。在接触HDM的新生小鼠和患有STRA的儿童的支气管内活检中，IL-33保持不变，而IL-13被类固醇治疗取消。IL-33是一种相对类固醇抵抗的介质，可促进STRA的气道重塑，是一个重要的治疗靶点。
Th2 cytokines are not responsible for the on-going symptoms and pathology in children with severe therapy resistant asthma (STRA). Interleukin (IL)-33 induces airway hyperresponsiveness (AHR), but its role in airway remodelling and steroid resistance is unknown. To investigate the relationship between IL-33 and airway remodelling in paediatric STRA. IL-33 was quantified in neonatal mice given inhaled house dust mite (HDM), and the effect of blocking IL-13 on remodelling and IL-33 was assessed. HDM induced allergic airways disease (AAD) in neonatal ST2−/− mice lacking the IL-33 receptor was assessed, together with collagen production following IL-33 administration. Impact of steroid therapy on IL-33 levels in neonatal AAD was explored. IL-33 expression was quantified in endobronchial biopsies from children with STRA and related to remodelling, and collagen production by paediatric airway fibroblasts stimulated with IL-33 and budesonide quantified. Blocking IL-13 after AAD was established in neonatal mice did not reduce remodelling or IL-33 levels; AHR was only partially reduced. IL-33 promoted collagen synthesis both from paediatric asthmatic fibroblasts, and following intra-nasal administration in mice. Increased cellular expression of IL-33, but not IL-13, was associated with increased reticular basement membrane thickness in endobronchial biopsies from children with STRA, whilst remodelling was absent in HDM exposed ST2−/− mice. IL-33 was maintained whilst IL-13 was abrogated by steroid treatment in neonatal HDM exposed mice, and in endobronchial biopsies from children with STRA. IL-33 is a relatively steroid resistant mediator that promotes airway remodelling in STRA, and is an important therapeutic target.
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DOI：
10.1164/rccm.200305-650oc
发表时间：
2003-10-01
影响因子：
24.7
作者：
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10.1164/rccm.200311-1488oc
发表时间：
2004-10-15
影响因子：
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DOI：
10.3904/kjim.2008.23.4.176
发表时间：
2008-12
期刊：
The Korean journal of internal medicine
影响因子：
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