Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Am J Respir Crit Care Med. 2012 Mar 15;185(6):620-7. doi: 10.1164/rccm.201108-1503OC. Epub 2012 Jan 12.
Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma.
Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage (BAL) from 39 subjects comprising three phenotypic groups (nonatopic nonasthmatic, atopic nonasthmatic, and atopic asthmatic) 4 hours after instillation of LPS, house dust mite antigen, and saline in three distinct subsegmental bronchi. RNA transcript levels were assessed using whole genome microarrays.
Baseline (saline exposure) differences in gene expression were related to airflow obstruction in epithelial cells (C3, ALOX5AP, CCL18, and others), and to serum IgE (innate immune genes and focal adhesion pathway) and allergic-asthmatic phenotype (complement genes, histone deacetylases, and GATA1 transcription factor) in inflammatory cells. LPS stimulation resulted in pronounced transcriptional response across all subjects in both airway epithelia and BAL cells, with strong association to nuclear factor-κB and IFN-inducible genes as well as signatures of other transcription factors (NRF2, C/EBP, and E2F1) and histone proteins. No distinct transcriptional profile to LPS was observed in the asthma and atopy phenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dust mite antigen stimulation, we observed subtle differences in gene expression (e.g., GATA1 and GATA2) in BAL cells related to the asthma and atopy phenotype.
Our results indicate that among individuals with allergic asthma, transcriptional changes in airway epithelia and inflammatory cells are influenced by phenotype as well as environmental exposures.
气道上皮和炎症细胞的基因表达谱可用于鉴定参与环境性哮喘的基因。
通过支气管刷检和支气管肺泡灌洗（BAL）从 39 例受试者中获得气道上皮细胞和炎症细胞，这些受试者包括三个表型组（非特应性非哮喘、特应性非哮喘和特应性哮喘），在三个不同的亚段支气管中，在 LPS、屋尘螨抗原和盐水注入 4 小时后。使用全基因组微阵列评估 RNA 转录水平。
上皮细胞中（C3、ALOX5AP、CCL18 等），基线（盐水暴露）差异的基因表达与气流阻塞有关，而炎症细胞中则与血清 IgE（先天免疫基因和黏附途径）和过敏-哮喘表型（补体基因、组蛋白去乙酰化酶和 GATA1 转录因子）有关。LPS 刺激导致所有受试者的气道上皮和 BAL 细胞中均出现明显的转录反应，与核因子-κB 和 IFN 诱导基因以及其他转录因子（NRF2、C/EBP 和 E2F1）和组蛋白蛋白的特征强烈相关。在哮喘和特应性表型中，未观察到 LPS 的独特转录谱。最后，尽管在对屋尘螨抗原刺激的所有受试者中未观察到一致的表达变化，但我们观察到 BAL 细胞中与哮喘和特应性表型相关的基因表达（例如 GATA1 和 GATA2）存在细微差异。
我们的结果表明，在患有过敏性哮喘的个体中，气道上皮和炎症细胞的转录变化受表型以及环境暴露的影响。
