Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells
Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells
复制标题
IL-17A 和 IL-25 在人鼻上皮细胞 TSLP 产生调节中的相反作用。
DOI：
10.1111/j.1398-9995.2009.02252.x
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发表时间：
2010-05-01
期刊：
影响因子：
12.4
通讯作者：
Li, H. B.
中科院分区：
文献类型：
--
作者：
Xu, G.;Zhang, L.;Li, H. B.
背景资料：IL-17 A、IL-17 F和IL-25在变应性鼻炎（AR）中的重要性及其在调节鼻上皮细胞胸腺基质淋巴细胞生成素（TSLP）产生中的可能作用尚不清楚。采用酶联免疫吸附试验（ELISA）检测AR患者鼻灌洗液中IL-17 A、IL-17 F、IL-25和TSLP水平，并与正常对照组进行比较。然后，用dsRNA（0-75 μ g/ml）以及IL-17 A（100 ng/ml）、IL-17 F（100 ng/ml）和IL-25（100 ng/ml）刺激原代人鼻上皮细胞（HNEC）。采用实时荧光定量PCR检测IL-17 A、IL-17 F、IL-25、TSLP以及趋化因子CCL 20、IL-8和eotaxin的mRNA表达，ELISA检测HNECs培养上清中上述因子的蛋白水平。发现dsRNA增加HNEC中IL-17 F、IL-25、TSLP、CCL 20和IL-8的产生。此外，IL-25显着增强dsRNA诱导的TSLP生产在原代HNECs和占主导地位的抑制作用IL-17 A对TSLP regulation.Conclusions：我们的研究提供了第一个证据表明，IL-17 F和IL-25可以诱导dsRNA在HNECs。尽管IL-17 A和IL-25对HNEC中TSLP调节的作用相反，但IL-25对IL-17 A占主导地位，为AR患者中IL-17细胞因子和TSLP的同时上调提供了合理的解释。
Background: The importance of IL-17A, IL-17F, and IL-25 in allergic rhinitis (AR), as well as their possible role in regulation on thymic stromal lymphopoietin (TSLP) production in nasal epithelial cells, is not well understood.Objective: To determine the possible regulation of IL-17A, IL-17F, and IL-25 on TSLP production in the initiation of allergic responses.Methods: The levels of IL-17A, IL-17F, IL-25, and TSLP in nasal lavages of patients with AR were measured using an enzyme-linked immunosorbent assay (ELISA) and compared with that in normal controls. Then, primary human nasal epithelial cells (HNECs) were stimulated with dsRNA (0-75 mu g/ml), as well as IL-17A (100 ng/ml), IL-17F (100 ng/ml), and IL-25(100 ng/ml). The mRNA expression of IL-17A, IL-17F, IL-25, TSLP, as well as the chemokines CCL20, IL-8, and eotaxin was analyzed using quantitative real-time PCR, and their protein levels in the supernatants of cultured HNECs were determined by ELISA.Results: Both TSLP and IL-17 cytokines are significantly elevated in patients with AR. dsRNA was found to increase the production of IL-17F, IL-25, TSLP, CCL20, and IL-8 in HNECs. Furthermore, IL-25 significantly enhanced dsRNA-induced TSLP production in primary HNECs and was dominant to the inhibitory effect of IL-17A on TSLP regulation.Conclusions: Our study provides the first evidence that both IL-17F and IL-25 can be induced by dsRNA in HNECs. Despite of the opposing effects of IL-17A and IL-25 on TSLP regulation in HNECs, IL-25 was dominant to IL-17A, providing a plausible explanation for the simultaneous upregulation of IL-17 cytokines and TSLP in patients with AR.