Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma
Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma
复制标题
DOI：
10.1067/mai.2002.124656
复制
发表时间：
2002-06-01
影响因子：
14.2
通讯作者：
Izuhara, K
中科院分区：
文献类型：
--
作者：
Arima, K;Umeshita-Suyama, R;Izuhara, K
背景：大量证据支持IL-13在哮喘发病机制中的关键作用。我们最近发现了IL-13基因的一个变异体(Arg110Gln)与哮喘的遗传相关，这与使用IL-13在哮喘发病中的动物实验是一致的。目的：为了研究IL-13的Gln110变异体是否影响IL-13的功能，从而参与哮喘的发病机制，我们研究了该变异体的功能特性。方法：我们构建了两种类型的重组IL-13蛋白，110位氨基酸为精氨酸或谷氨酰胺，并分析了其与IL-13受体的结合亲和力以及蛋白的稳定性。进一步比较IL-13基因分型与血清IL-13水平的关系。结果：该变异体与诱骗受体IL-13受体α2链亲和力较低，清除率较低。该变异体在人和小鼠血浆中也显示出增强的稳定性。进一步研究发现，Gln110纯合子哮喘患者的血清IL-13水平高于无Gln110纯合子哮喘患者。结论：Gln110纯合子哮喘患者体内局部和全身IL-13水平升高可能是一种功能性遗传因素。
Background: A substantial body of evidence exists to support the pivotal role of IL-13 in the pathogenesis of bronchial asthma. We recently found that a variant of the IL13 gene (Arg110Gln) is genetically associated with bronchial asthma, which is concordant with animal experiments using IL-13 in the development of asthma.Objective: To address whether the Gln110 variant of IL13 influences IL-13 function, contributing to the pathogenesis of bronchial asthma, we studied the functional properties of the variant.Methods: We generated 2 types of recombinant IL-13 proteins, the amino acids of which at 110 were arginine or glutamine, and analyzed the binding affinities with the IL-13 receptors, as well as the stability of the proteins. We further compared the relationship between the genotype and serum levels of IL-13.Results: The variant showed a lower affinity with the IL-13 receptor alpha2 chain, a decoy receptor, causing less clearance. The variant also demonstrated an enhanced stability in both human and mouse plasma. We further identified that asthmatic patients homozygous for the Gln110 variant have higher serum levels of IL-13 than those without the variant.Conclusion: These results suggested that the variant might act as a functional genetic factor of bronchial asthma with a unique mechanism to upregulate local and systemic IL-13 concentration in vivo.