揭示了upre TY - T1的转录组分析gulation of bitter taste receptors in severe asthmatics JF - European Respiratory Journal JO - Eur Respir J SP - 65 LP - 78 DO - 10.1183/09031936.00077712 VL - 42 IS - 1 AU - Orsmark-Pietras, Christina AU - James, Anna AU - Konradsen, Jon R. AU - Nordlund, Björn AU - Söderhäll, Cilla AU - Pulkkinen, Ville AU - Pedroletti, Christophe AU - Daham, Kameran AU - Kupczyk, Maciek AU - Dahlén, Barbro AU - Kere, Juha AU - Dahlén, Sven-Erik AU - Hedlin, Gunilla AU - Melén, Erik Y1 - 2013/07/01 UR - //www.qdcxjkg.com/content/42/1/65.abstract N2 - The causes of severe childhood asthma are poorly understood. Our aim was to define global patterns of gene expression in children with severe therapy-resistant and controlled asthma. White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip in children with severe, therapy-resistant asthma (n=17), controlled asthma (n=19) and healthy controls (n=18). Receptor expression was studied in separated leukocyte fractions from asthmatic adults (n=12). Overall, 1378 genes were differentially expressed between children with severe/controlled asthma and controls. Three significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were represented: natural killer cell-mediated cytotoxicity (upregulated in controlled asthma); N-glycan biosynthesis (downregulated in severe asthma); and bitter taste transduction receptors (TAS2Rs) (upregulated in severe asthma). Quantitative PCR experiments confirmed upregulation of TAS2Rs in severe asthmatics. TAS2R expression was replicated in leukocytes from adult asthmatics, in which TAS2R agonists also inhibited LPS-induced cytokine release. Significant correlations between expression of TAS2Rs and clinical markers of asthma severity were found in both adults and children. In conclusion, specific gene expression patterns were observed in children with severe, therapy-resistant asthma. The increased expression of bronchodilatory TAS2Rs suggests a new target for the treatment of asthma. ER -