Effects of allergen challenge on airway epithelial cell gene expression
Effects of allergen challenge on airway epithelial cell gene expression
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DOI：
10.1164/rccm.200404-532oc
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发表时间：
2005-03-15
影响因子：
24.7
通讯作者：
Sonna, LA
中科院分区：
文献类型：
--
作者：
Lilly, CM;Tateno, H;Sonna, LA
变应原暴露诱导气道上皮产生化学引诱剂、促变应性白细胞介素、基质修饰蛋白和影响气道结构细胞生长和活化状态的蛋白质。反过来，这些蛋白质有助于炎症细胞的流入和哮喘气道结构的变化。使用过敏原的气道上皮细胞的反应，以确定以前不与过敏反应相关的基因，我们比较了细胞角蛋白阳性细胞的基因表达之前和之后的节段性过敏原的挑战。在用临床相关范围内的过敏原浓度进行攻击后，755个（6%）可检测序列的表达具有几何平均倍数变化，95%置信区间排除了统一性。使用一个前瞻性定义的保守过滤算法，我们确定了141个序列上调和8个下调，与常规的聚合酶链反应在所有10个序列研究的确认。使用这种方法，我们确定了哮喘相关序列，包括白细胞介素（IL-）-3，IL-4和IL-5受体亚单位，核因子-κ B的p65组分和脂皮质素。人类气道对临床相关范围内过敏原浓度的基因组反应涉及比以前认识到的更多的基因，包括许多以前与哮喘无关的在气道过敏原暴露后差异表达的基因。
Allergen exposure induces the airway epithelium to produce chemo-attractants, proallergic interieukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interieukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappa B, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure.