Effect of Genetic Variation of IL-13 on Airway Remodeling in Bronchial Asthma
Effect of Genetic Variation of IL-13 on Airway Remodeling in Bronchial Asthma
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DOI：
10.2332/allergolint.10-oa-0259
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发表时间：
2011-09-01
影响因子：
6.8
通讯作者：
Yamauchi, Kohei
中科院分区：
文献类型：
--
作者：
Nagashima, Hiromi;Nakamura, Yutaka;Yamauchi, Kohei
背景资料：IL-13是Th 2炎症部位的炎症和组织重塑的主要刺激物，IL-13中常见的单核苷酸多态性与几个不同种族人群中的过敏表型相关。特别地，IL 13 Q110是在IL-13的位置110处用中性谷氨酰胺（Q）非保守地替换带正电荷的精氨酸（R），并且如我们已经知道的，谷氨酰胺纯合子（Q110/Q110）的个体与哮喘和IgE强烈相关。已经证明IL 13 Q110显示增加的过敏性炎症依赖于增强的IL-13介导的Th 2效应子功能。因此，我们调查是否Q110/Q110加速肺功能的下降和哮喘患者在一般population.Methods的气道重塑的发展：共336名哮喘患者生活在日本招募，基因分型，并进行肺功能测试。为了分析气道炎症和重塑，检查了支气管灌洗液（BLF）和支气管内活检标本。与R110/R110相比，Q110/Q110的一秒用力呼气量（FEV 1）、%预测值、用力呼气量/用力肺活量比值和用力呼气流量25- 75%、%预测值显著降低，Q110/Q110组FEV 1下降幅度较R110/R110组明显增大。IL-13，IL-23，IL-11，GM-CSF，透明质酸，和CCL 8在BLF的浓度增加Q110/Q110相比，R110/R110和上皮下层的厚度thicken.Conclusions：我们的研究表明，Q110/Q110增加，至少部分，过敏性炎症和气道重塑的倾向，从而导致低肺功能。
Background: IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13Q110 is the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 110 of IL-13, and as we already know, individuals homozygous for glutamine (Q110/Q110) are strongly associated with asthma and IgE. IL13Q110 has been demonstrated to show that increased allergic inflammation depended on the enhanced IL-13-mediated Th2 effector function. Therefore, we investigated whether Q110/Q110 accelerated the decline in pulmonary function and development of airway remodeling of asthmatic patients in the general population.Methods: A total 336 asthmatic subjects living in Japan were recruited, genotyped, and had a pulmonary function test performed on them. To analyze airway inflammation and remodeling, bronchial lavage fluid (BLF) and endobronchial biopsy specimens were examined.Results: Forced expiratory volume in one second (FEV1), %predicted, forced expiratory volume/forced vital capacity ratio, and forced expiratory flow 25-75%, % predicted were significantly decreased in Q110/Q110 compared to R110/R110, and the decline in FEV1 was increased significantly in Q110/Q110 compared to R 110/R110. The concentration of IL-13, IL-23, IL-11, GM-CSF, hyaluronic acid, and CCL8 in BLF were increased in Q110/Q110 compared to R110/R110 and the thickness of the subepithelial layer was thicker.Conclusions: Our study demonstrates that Q110/Q110 increases, at least in part, allergic inflammation and the propensity for airway remodeling, thus resulting in low lung function.