title: Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics.
abstract: 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.
authors.affiliation: Dept of Biosciences and Nutrition at Novum, Karolinska Institute, Stockholm, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Orsmark-Pietras
authors.forename: Anna
authors.initials: A
authors.lastname: James
authors.forename: Jon R
authors.initials: JR
authors.lastname: Konradsen
authors.forename: Björn
authors.initials: B
authors.lastname: Nordlund
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
authors.forename: Christophe
authors.initials: C
authors.lastname: Pedroletti
authors.forename: Kameran
authors.initials: K
authors.lastname: Daham
authors.forename: Maciek
authors.initials: M
authors.lastname: Kupczyk
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Gunilla
authors.initials: G
authors.lastname: Hedlin
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013548:Sweden; D013649:Taste / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D009569:Nitric Oxide