Expression of interleukin-13 receptor α 1-subunit on peripheral blood eosinophils is regulated by cytokines
Expression of interleukin-13 receptor α 1-subunit on peripheral blood eosinophils is regulated by cytokines
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DOI：
10.1046/j.1365-2567.2004.01897.x
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发表时间：
2004-08-01
期刊：
影响因子：
6.4
通讯作者：
Luttmann, W
中科院分区：
文献类型：
--
作者：
Myrtek, D;Knoll, M;Luttmann, W
白介素 13 (IL-13) 对于过敏性哮喘的发生至关重要，并参与气道内嗜酸性粒细胞的激活。 IL-13 通过二聚体 IL-13 受体 (IL-13R) 对靶细胞发挥活性，二聚体 IL-13 受体 α1 链 (IL-13Rα1) 作为特定成分。本研究的目的是研究原代人嗜酸性粒细胞上 IL-13Rα1 链的表达。此外，它还解决了细胞因子对该受体亚基表面丰度水平的调节影响。通过逆转录聚合酶链式反应在信使RNA水平上监测纯化的原代人嗜酸性粒细胞中IL-13-和IL-4-受体亚基的表达，并通过流式细胞术在蛋白质水平上监测。为了分析 IL-13Rα1 表面表达，采用了通过基因免疫产生的新单克隆抗体。通过流式细胞术研究了对嗜酸性粒细胞具有确定活性的不同细胞因子在体外对 IL-13Ralpha1 的影响。而IL-13和IL-4对嗜酸性粒细胞上的IL-13Rα1表达具有抑制作用，干扰素-γ、肿瘤坏死因子-α以及最大程度的转化生长因子-β增强了该受体亚基的表达。转化生长因子-β 和干扰素-γ 引起的积极调节反应并不能阻止 IL-13 引起的抑制作用。这些发现表明调节性细胞因子网络影响嗜酸性粒细胞对 IL-13 的反应性。
Interleukin-13 (IL-13) is critical for the development of allergic asthma and is involved in the activation of eosinophils within the airways. IL-13 exerts its activity on target cells via the dimeric IL-13 receptor (IL-13R), which comprises the IL-13 receptor alpha1-chain (IL-13Ralpha1) as a specific component. The aim of this study was to investigate the expression of the IL-13Ralpha1-chain on primary human eosinophilic granulocytes. Furthermore, it addresses the regulatory influence of cytokines on the level of surface abundance of this receptor subunit. Expression of IL-13- and IL-4-receptor subunits in purified primary human eosinophils was monitored at the messenger RNA level by reverse transcription polymerase chain reaction and at the protein level by flow cytometry. For the analysis of IL-13Ralpha1 surface expression, a new monoclonal antibody, which was generated using genetic immunization, was employed. Different cytokines with established activity on eosinophils were studied with regard to their influence on IL-13Ralpha1 in vitro by flow cytometry. Whereas IL-13 and IL-4 had inhibitory effects on IL-13Ralpha1 expression on eosinophils, interferon-gamma, tumour necrosis factor-alpha, and, to the largest extent, transforming growth factor-beta, enhanced the expression of this receptor subunit. A positive regulatory response evoked by transforming growth factor-beta and interferon-gamma does not prevent inhibitory effects caused by IL-13. These findings suggest a regulatory cytokine network influencing the reactivity of eosinophils to IL-13.