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Molecular mechanisms of chemokine gene expression in allergic airway inflammation : Selective induction of eotaxin and TARC by Th2 cytokines in airway epithelial cells

过敏性气道炎症趋化因子基因表达的分子机制：气道上皮细胞中Th2细胞因子选择性诱导eotaxin和TARC

基本信息

批准号：
12670551
负责人：
TAKIZAWA Hajime
金额：
$ 2.18万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Airway epithelium-drived chemokines are believed to play important roles in the pathogenesis of allergic airway inflammatory diseases such as bronchial asthma. However, it remains unclear how certain chemokines are predominant in such airway inflammation ; for example, eosinophils in asthma and neutrophils in chrnic bronchitis, respectively. We studied the effect of Th-2 type cytokines such as IL-4 and IL-13 in the selective upregulation in chemokine gene expression in airway epithelial cells. We found that IL-4 and IL-13 both stimulated eotaxin gene expression, which is considered to be crucial in eosinophil recruitment in the airways. In contrast, these Th2 cytokines downregulated IL-8 gene expression, which is well known to be a potent neutrophil chemoattaractant. Further, IL-13 clearly induced STAT6 activation, an important step for the eotaxin transcription, but downregulated NFκB transcativation. Airway epithelial cells harvested from asthmatic subjects after informed consent, tended to show more eotaxin production than those from normal and bronchitis patients. These observations demonstrated that Th2 cytokines may play an important role in the selective induction of certain chemokines in allergic airway inflmmation.

气道上皮细胞趋化因子被认为在支气管哮喘等过敏性气道炎性疾病的发病机制中起重要作用。然而，目前还不清楚某些趋化因子是如何在这种气道炎症中占主导地位的;例如，哮喘中的嗜酸性粒细胞和慢性支气管炎中的嗜中性粒细胞。我们研究了Th-2型细胞因子如IL-4和IL-13在选择性上调气道上皮细胞趋化因子基因表达中的作用。我们发现，IL-4和IL-13都刺激嗜酸性粒细胞趋化因子基因的表达，这被认为是至关重要的嗜酸性粒细胞在气道的招聘。相反，这些Th 2细胞因子下调IL-8基因的表达，这是众所周知的是一个强大的中性粒细胞趋化因子。此外，IL-13明显诱导STAT 6活化，这是嗜酸性粒细胞趋化因子转录的重要步骤，但下调NFκB转录激活。在知情同意后从哮喘受试者中采集的气道上皮细胞倾向于显示出比正常和支气管炎患者更多的嗜酸性粒细胞趋化因子产生。这些结果表明，Th 2细胞因子可能在某些趋化因子的选择性诱导过敏性气道炎症中起重要作用。