IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.
IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.
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DOI：
10.1371/journal.pone.0054623
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hoshino T
中科院分区：
文献类型：
--
作者：
Sawada M;Kawayama T;Imaoka H;Sakazaki Y;Oda H;Takenaka S;Kaku Y;Azuma K;Tajiri M;Edakuni N;Okamoto M;Kato S;Hoshino T
IL-18在肺部炎症性疾病包括肺部感染、肺纤维化、肺损伤和慢性阻塞性肺疾病（COPD）的发病机制中发挥着关键作用。然而，IL-18 在哮喘发病机制中是否发挥作用尚不清楚。我们假设肺部成熟 IL-18 蛋白的过度表达可能会加剧哮喘的疾病活动。我们在 Balb/c 遗传背景上建立了肺特异性 IL-18 转基因小鼠。用抗原（卵清蛋白）致敏和激发的雌性小鼠被用作小鼠哮喘模型。在幼稚转基因小鼠的肺部没有观察到肺部炎症和肺气肿。然而，与野生型Balb/c小鼠相比，在卵清蛋白致敏和攻击的转基因小鼠中，气道高反应性和气道炎症细胞伴随CD4+T细胞、CD8+T细胞、嗜酸性粒细胞、中性粒细胞和巨噬细胞显着增加。我们还证明，IL-18 在卵清蛋白致敏和受攻击的转基因小鼠的肺部诱导 IFN-γ、IL-13 和嗜酸粒细胞趋化因子，同时增加产生 IL-13 的 CD4+ T 细胞。使用抗 CD4 单克隆抗体治疗或删除 IL-13 基因可改善转基因小鼠中卵清蛋白诱导的气道高反应性并减少气道炎症细胞。肺部过度表达 IL-18 蛋白会诱导 1 型和 2 型细胞因子和气道炎症，并通过哮喘中的 CD4+ T 细胞和 IL-13 导致气道高反应性增加。
IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized– and challenged– with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4+ T cells, CD8+ T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4+ T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4+ T cells and IL-13 in asthma.
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DOI：
10.1165/rcmb.2003-0306oc
发表时间：
2004-12-01
影响因子：
6.4
作者：
Kitasato, Y;Hoshino, T;Aizawa, H
通讯作者：
Aizawa, H
影响因子：
4.4
作者：
Hoshino, T;Kawase, Y;Oizumi, K
通讯作者：
Oizumi, K
DOI：
10.1165/rcmb.2008-0182oc
发表时间：
2009-12
影响因子：
6.4
作者：
通讯作者：
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DOI：
10.1164/rccm.200603-316oc
发表时间：
2007-07-01
影响因子：
24.7
作者：
Hoshino, Tomoaki;Kato, Seiya;Aizawa, Hisamichi
通讯作者：
Aizawa, Hisamichi
影响因子：
158.5
作者：
Corren, Jonathan;Lemanske, Robert F., Jr.;Matthews, John G.
通讯作者：
Matthews, John G.