Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells.
Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells.
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DOI：
10.1152/ajplung.00422.2009
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
S. White;Linda D. Martin;R. Stern;B. Laxman;B. Marroquin
中科院分区：
文献类型：
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作者：
S. White;Linda D. Martin;R. Stern;B. Laxman;B. Marroquin
IL-4和IL-13在气道上皮中引起几种重要的反应，包括可能有助于气道炎症、细胞迁移和分化的趋化因子分泌和粘液分泌。这些细胞因子具有重叠但不相同的效应物谱，可能是由于它们的受体复合物中共有的亚基。这些受体在上皮细胞中被广泛描述，并且这些受体在分化和修复上皮细胞中的相对表达、定位和功能尚不清楚。我们研究了IL-4/IL-13受体的表达和定位在原代气道上皮细胞收集正常人肺和生长条件下产生未分化和分化的细胞，包括基底，杯状和纤毛细胞表型。IL-4 R α、IL-2 R γc、IL-13 R α1和IL-13 R α2受体亚基的基因表达随着分化而增加，但基于分化和存在的细胞亚型，每个亚基的定位和蛋白丰度模式不同。在分化程度更高的细胞中观察到的受体亚单位表达增加与对IL-4刺激的更实质性功能反应相关，包括损伤后嗜酸性粒细胞趋化因子-3表达增加和迁移加速。我们证明了基于气道上皮细胞分化程度的IL-4/IL-13受体亚基表达和对IL-4的反应性的实质性差异，并表明这些差异可能在气道炎症中具有功能性后果。
IL-4 and IL-13 elicit several important responses in airway epithelium including chemokine secretion and mucous secretion that may contribute to airway inflammation, cell migration, and differentiation. These cytokines have overlapping but not identical effector profiles likely due to shared subunits in their receptor complexes. These receptors are variably described in epithelial cells, and the relative expression, localization, and function of these receptors in differentiated and repairing epithelial cells are not clear. We examined IL-4/IL-13 receptor expression and localization in primary airway epithelial cells collected from normal human lungs and grown under conditions yielding both undifferentiated and differentiated cells inclusive of basal, goblet, and ciliated cell phenotypes. Gene expression of the IL-4Rα, IL-2Rγc, IL-13Rα1, and IL-13Rα2 receptor subunits increased with differentiation, but different patterns of localization and protein abundance were seen for each subunit based on both differentiation and the cell subtypes present. Increased expression of receptor subunits observed in more differentiated cells was associated with more substantial functional responses to IL-4 stimulation including increased eotaxin-3 expression and accelerated migration after injury. We demonstrate substantial differences in IL-4/IL-13 receptor subunit expression and responsiveness to IL-4 based on the extent of airway epithelial cell differentiation and suggest that these differences may have functional consequences in airway inflammation.