IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2
IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2
复制标题
DOI：
10.1007/pl00000233
复制
发表时间：
2001-11-01
影响因子：
6.7
通讯作者：
Hogaboam, CM
中科院分区：
文献类型：
--
作者：
Blease, K;Kunkel, SL;Hogaboam, CM
真菌诱发的哮喘疾病的特征是持续的气道高反应性和重塑。目的和设计：在烟曲霉诱发的哮喘小鼠模型中确定 IL-18 在烟曲霉分生孢子过敏性气道反应中的作用。方法：在烟曲霉致敏的小鼠产生分生孢子后 3 天，使用多克隆抗 IL-18 抗体去除 IL-18。结果：与正常血清处理组相比，分生孢子攻击后 3-30 天气道高反应性和嗜酸性粒细胞数量显着升高。组织学证据显示，在分生孢子攻击后第 30 天，IL-18 耗尽的小鼠肺部出现烟曲霉分生孢子滞留、气道重塑、上皮下纤维化和胶原沉积增加。与对照组相比，IL-18 耗尽的 A. Jumigatus 致敏小鼠的分生孢子保留时间延长与 Toll 样受体 2 (TLR-2) 表达降低有关。结论：IL-18 调节针对烟曲霉分生孢子的先天免疫反应，并预防严重真菌诱发的哮喘病的发展。
Fungus-induced asthmatic disease is characterized by persistent airway hyperreactivity and remodeling.Objective and design: To determine the role of IL-18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatus-induced asthma.Methods: A. fumigatus-sensitized mice were depleted of IL-18 using a polyclonal anti-IL-18 antibody for 3 days after a conidia challenge.Results: Airway hyperresponsiveness and eosinophil numbers were significantly elevated 3-30 days after conidia challenge compared to the normal serum-treated group. Histological evidence showed retention of A. fumigatus conidia, airway remodeling, subepithelial fibrosis, and increased collagen deposition in the lungs of IL-18-depleted mice at day 30 after the conidia challenge. Prolonged retention of conidia in IL-18 depleted A. Jumigatus-sensitized mice was associated with decreased Toll-like receptor-2 (TLR-2) expression compared with the control group.Conclusions: IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease.