IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells
IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells
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DOI：
10.4049/jimmunol.173.4.2771
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Shan, LY
中科院分区：
文献类型：
--
作者：
Gounni, AS;Hamid, Q;Shan, LY
最近的研究表明IL-9在过敏性疾病中的潜在重要性。过度表达IL-9的转基因小鼠的发展表明这种细胞因子在哮喘表型包括气道嗜酸性粒细胞增多症的发展中起关键作用。在这项研究中，我们评估了IL-9 R的表达和IL-9对人ASM细胞的影响，通过检查释放的Th 2相关的趋化因子（嗜酸性粒细胞趋化因子1/CCL 11和胸腺和活化调节趋化因子（TARC）/CCL 17）。在培养的人气道平滑肌（ASM）细胞中检测IL-9 R α链mRNA和表面表达。此外，原代培养的ASM细胞，以及支气管平滑肌细胞内活检的哮喘，而不是对照组，揭示了IL-9 R蛋白的表达。IL-9刺激人ASM细胞可导致Eotaxin 1/CCL 11的释放，但对TARC/CCL 17的释放无影响，且呈时间和剂量依赖性。此外，体外趋化实验表明，条件培养基从IL-9刺激的ASM细胞吸引人嗜酸性粒细胞。针对IL-9而非IL-4或IL-13的中和Ab显著降低了IL-9诱导的ASM细胞中eotaxin 1/CCL 11的产生。有趣的是，实时RT-PCR显示IL-9上调eotaxin 1/CCL 11 mRNA的表达，但对TARC/CCL 17没有影响。用Act D处理废除了ASM细胞的IL-9诱导的eotaxin 1/CCL 11 mRNA和蛋白质释放。最后，使用eotaxin 1/CCL 11启动子荧光素酶构建体的转染研究证实了IL-9在转录水平上诱导eotaxin 1/CCL 11。总之，这些数据提供了新的证据，表明ASM细胞的IL-9依赖性激活有助于在哮喘中观察到的嗜酸性粒细胞炎症。
Recent work has shown the potential importance of IL-9 in allergic diseases. The development of transgenic mice overexpressing IL-9 has suggested a key role for this cytokine in the development of the asthmatic phenotype including airway eosinophilia. In this study, we evaluated the expression of the IL-9R and the effects of IL-9 on human ASM cells by examining the release of Th2-associated chemokines (eotaxin1/CCL11 and thymus- and activation-regulated chemokine (TARC)/CCL17). IL-9R alpha-chain mRNA and surface expression were detected in cultured human airway smooth muscle (ASM) cells. In addition, primary cultured ASM cells, as well as bronchial smooth muscle cells within biopsies of asthmatics and not control subjects, revealed IL-9R protein expression. IL-9 stimulation of human ASM cells resulted in release of eotaxin1/CCL11, but had no effect on the release of TARC/CCL17, in time- and dose-dependent manner. Moreover, in vitro chemotaxis assay demonstrated that conditioned medium from IL-9-stimulated ASM cells attracted human eosinophils. Neutralizing Abs to IL-9, but not to IL-4 or IL-13, reduced significantly IL-9-induced production of eotaxin1/CCL11 from ASM cells. Interestingly, real-time RT-PCR showed that IL-9 up-regulated eotaxin1/CCL11 mRNA expression, but had no effect on TARC/CCL17. Treatment with Act D abrogates IL-9-induced eotaxin1/CCL11 mRNA and protein release by ASM cells. Finally, transfection study using eotaxin1/CCL11 promoter luciferase construct confirmed that IL-9 induced eotaxin1/CCL11 at the transcriptional level. Taken together, these data provide new evidence demonstrating that IL-9-dependent activation of ASM cells contributes to eosinophilic inflammation observed in asthma.