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Abstract：
UNASSIGNED: In asthma, genome-wide association studies have shown that interleukin-18 (IL-18) receptor 1 gene (IL-18R1) and sputum IL-18 are increased during exacerbations. However, the role of the IL-18 axis in bronchial epithelial function is unclear. To investigate IL-18, IL-18 binding protein (BP) and IL-18R expression in bronchial biopsies and sputum samples from patients with asthma, and to determine its functional role using in vitro bronchial epithelial cells.
UNASSIGNED: The expression of IL-18, IL-18BP and IL-18Rα was examined in subjects with asthma and healthy controls in bronchial biopsies by immunohistochemistry and IL-18 and IL-18BP release in sputum. In epithelial cells, the mRNA and protein expression of IL-18, IL-18BP, IL-18Rα and IL-18Rβ was assessed by qPCR, flow cytometry, Western blotting and immunofluorescence respectively. IL-18 function in epithelial cells was examined by intracellular calcium, wound repair, synthetic activation and epithelial differentiation changes.
UNASSIGNED: In biopsies from subjects with asthma, the IL-18 expression was not different in the lamina propria compared with controls but was decreased in the epithelium. In contrast, the IL-18BP was decreased in the lamina propria in asthma and was absent in the bronchial epithelium. IL-18 was released in sputum with IL-18BP elevated in patients with asthma. The IL-18Rα expression was not different between health and disease. In vitro, IL-18-stimulated bronchial epithelial cells increased intracellular calcium, wound repair, metabolic activity, morphological changes and epithelial cellular differentiation.
UNASSIGNED: In asthma, the dynamic interaction between IL-18, its cognate receptor and natural inhibitor is complex, with differences between airway compartments. Upregulation of IL-18 can promote epithelial activation and cellular differentiation.
UNASSIGNED: The expression of IL-18, IL-18BP and IL-18Rα was examined in subjects with asthma and healthy controls in bronchial biopsies by immunohistochemistry and IL-18 and IL-18BP release in sputum. In epithelial cells, the mRNA and protein expression of IL-18, IL-18BP, IL-18Rα and IL-18Rβ was assessed by qPCR, flow cytometry, Western blotting and immunofluorescence respectively. IL-18 function in epithelial cells was examined by intracellular calcium, wound repair, synthetic activation and epithelial differentiation changes.
UNASSIGNED: In biopsies from subjects with asthma, the IL-18 expression was not different in the lamina propria compared with controls but was decreased in the epithelium. In contrast, the IL-18BP was decreased in the lamina propria in asthma and was absent in the bronchial epithelium. IL-18 was released in sputum with IL-18BP elevated in patients with asthma. The IL-18Rα expression was not different between health and disease. In vitro, IL-18-stimulated bronchial epithelial cells increased intracellular calcium, wound repair, metabolic activity, morphological changes and epithelial cellular differentiation.
UNASSIGNED: In asthma, the dynamic interaction between IL-18, its cognate receptor and natural inhibitor is complex, with differences between airway compartments. Upregulation of IL-18 can promote epithelial activation and cellular differentiation.
摘要：
■在哮喘中，全基因组关联研究表明,白细胞介素-18(IL-18)受体1基因(IL-18R1)和痰液IL-18在加重期增加.然而,IL-18轴在支气管上皮功能中的作用尚不清楚.探讨哮喘患者支气管活检和痰标本中IL-18、IL-18结合蛋白(BP)和IL-18R的表达,并利用体外支气管上皮细胞确定其功能作用。
■通过免疫组织化学和痰中IL-18和IL-18BP的释放，在哮喘患者和健康对照者的支气管活检中检测IL-18，IL-18BP和IL-18Rα的表达。在上皮细胞中，IL-18、IL-18BP、通过qPCR评估IL-18Rα和IL-18Rβ，流式细胞术,分别进行蛋白质印迹和免疫荧光。IL-18在上皮细胞中的功能通过细胞内钙，伤口修复,合成激活和上皮分化变化。
■在哮喘患者的活检中，与对照组相比，固有层中的IL-18表达没有差异，但在上皮中降低。相比之下,哮喘患者固有层IL-18BP降低,支气管上皮IL-18BP缺失。哮喘患者痰中IL-18释放，IL-18BP升高。健康和疾病之间的IL-18Rα表达没有差异。体外，IL-18刺激的支气管上皮细胞增加细胞内钙，伤口修复,代谢活动，形态学改变和上皮细胞分化。
■在哮喘中，IL-18，其同源受体和天然抑制剂之间的动态相互作用是复杂的，气道隔室之间的差异。IL-18上调可促进上皮活化和细胞分化。
■通过免疫组织化学和痰中IL-18和IL-18BP的释放，在哮喘患者和健康对照者的支气管活检中检测IL-18，IL-18BP和IL-18Rα的表达。在上皮细胞中，IL-18、IL-18BP、通过qPCR评估IL-18Rα和IL-18Rβ，流式细胞术,分别进行蛋白质印迹和免疫荧光。IL-18在上皮细胞中的功能通过细胞内钙，伤口修复,合成激活和上皮分化变化。
■在哮喘患者的活检中，与对照组相比，固有层中的IL-18表达没有差异，但在上皮中降低。相比之下,哮喘患者固有层IL-18BP降低,支气管上皮IL-18BP缺失。哮喘患者痰中IL-18释放，IL-18BP升高。健康和疾病之间的IL-18Rα表达没有差异。体外，IL-18刺激的支气管上皮细胞增加细胞内钙，伤口修复,代谢活动，形态学改变和上皮细胞分化。
■在哮喘中，IL-18，其同源受体和天然抑制剂之间的动态相互作用是复杂的，气道隔室之间的差异。IL-18上调可促进上皮活化和细胞分化。
