Direct comparison of the dynamics of IL-25-and 'allergen'-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model
Direct comparison of the dynamics of IL-25-and 'allergen'-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model
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DOI：
10.1111/cea.12298
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发表时间：
2014-05-01
影响因子：
6.1
通讯作者：
Ying, S.
中科院分区：
文献类型：
--
作者：
Yao, X. J.;Huang, K. W.;Ying, S.
从人类哮喘患者和小鼠哮喘模型的研究中发现，白细胞介素-25与哮喘的发病机制有关。目的在本研究中，我们假设气道长期暴露于IL-25能够诱导哮喘动物模型中观察到的致病性变化。方法比较经典过敏性哮喘模型OVA致敏小鼠和单纯IL-25致敏小鼠的细胞浸润、细胞因子表达、气道重构和高反应性的动态变化。结果单纯IL-25经鼻刺激BALB/c小鼠，气道腔内嗜酸性细胞和淋巴细胞的浸润延迟（与ova刺激相比），th2型细胞因子、趋化因子和胶原的分泌增加，上皮粘液分泌增加，杯状细胞增生，上皮下胶原沉积，气道平滑肌细胞增生和血管生成。相应地，IL-25和OVA挑战均诱导气道高反应性和肺组织阻尼增加。相反，IL-25暴露不增加IgE或IgG(1)的产生。结论和临床意义数据表明，单独暴露于IL-25的慢性气道足以诱导不依赖于过敏原和ige的哮喘样气道炎症、重塑和高反应性。因此，无论是否存在ige依赖机制，IL-25都是哮喘的关键分子靶点。
BackgroundInterleukin-25 has been implicated in the pathogenesis of asthma from studies on human asthmatics and in murine asthma models.ObjectivesIn this study, we hypothesized that chronic exposure of the airways to IL-25 alone is able to induce pathogenic changes observed in animal models of asthma.MethodsWe performed a detailed comparison of the dynamics of development of cellular infiltration, cytokine expression and airways remodelling and hyperresponsiveness in mice sensitized and challenged with OVA, a classical model of allergic asthma and those exposed to IL-25 alone.ResultsIntranasal challenge of BALB/c mice with IL-25 alone induced a delayed (compared with OVA-challenge), predominantly eosinophilic and lymphocytic infiltration into the airways lumen, along with increased production of Th2-type cytokines, chemokines and collagen, secretion of epithelial mucus, goblet cell hyperplasia, deposition of subepithelial collagen, airways smooth muscle cell hyperplasia and angiogenesis. Correspondingly, IL-25 as well as OVA challenge both induced airways hyperresponsiveness and increased lung tissue damping. In contrast, IL-25 exposure did not increase IgE or IgG(1) production.Conclusions and Clinical RelevanceThe data suggest that chronic airways exposure to IL-25 alone is sufficient to induce allergen- and IgE-independent, asthma-like airways inflammation, remodelling and hyperresponsiveness in mice. Thus, IL-25 is a key molecular target in asthma, irrespective of the coexistence of IgE-dependent mechanisms.