ABSTRACT: A comparison of GS-5759, a bifunctional β2-adrenoceptor agonist and PDE4 inhibitor, and indacaterol and GSK 256066 in combination on gene expression changes in the BEAS-2B human airway epithelial cell line
Project description:GS-5759 is a bifunctional ligand composed of a quinolinone-containing pharmacophore found in several β2-adrenoceptor agonists linked covalently to a phosphodiesterase 4 inhibitor (PDE4) related to GSK 256066 by a pent-1-yn-1-ylbenzene spacer. The object of the study was to detemine if gene expression changes induced by GS-5759 were replicated by a β2-adrenoceptor agonist (indacaterol; Ind) and a PDE4 inhibitor (GSK 256066; GSK) in combination. Microarray analysis was performed on RNA from BEAS-2B cells treated with GS-5759 and a combination of indacaterol and GSK 256066 to identify differentialy expressed genes.
Project description:GS-5759 is a bifunctional ligand composed of a quinolinone-containing pharmacophore found in several β2-adrenoceptor agonists linked covalently to a phosphodiesterase 4 inhibitor (PDE4) related to GSK 256066 by a pent-1-yn-1-ylbenzene spacer. The object of the study was to detemine if gene expression changes induced by GS-5759 were replicated by a β2-adrenoceptor agonist (indacaterol; Ind) and a PDE4 inhibitor (GSK 256066; GSK) in combination. Microarray analysis was performed on RNA from BEAS-2B cells treated with GS-5759 and a combination of indacaterol and GSK 256066 to identify differentialy expressed genes. Confluent BEAS-2B cells were treated with vehicle, Ind/GSK or GS-5759 for 1h, 2h, 6h or 18h. Total RNA was extracted, quantified (NanoDrop 2000) and the quality of each sample determined by using the Agilent 2100 Lab-on-a-Chip system before being processed for gene expression chnages by Expression Analysis Inc (Dunham, NC, USA).
Project description:Microarray analysis was performed on RNA extracted from BEAS-2B cells treated with indacaterol, GSK 256066 and indacaterol and GSK 256066 in combination to identify differentially expressed genes that may contribute to the beneficial and deleterious effects of β2-adrenoceptor agonists and phosphodiesterase 4 inhibitors in obstructive lung diseases.
Project description:In asthma, the clinical efficacy of inhaled corticosteroids (ICSs) is enhanced by long-acting β2-adrenoceptor agonists (LABAs). ICSs, or more accurately, glucocorticoids, promote therapeutically-relevant changes in gene expression and this genomic effect can be enhanced by a LABA. To investigate the gene expression changes by each condition, transcriptomic analysis was performed on RNA extracted from BEAS-2B cells treated with budesonide, formoterol, or both combined.
Project description:Gene expression analysis of human bronchial airway epithelial BEAS-2B cells stimulated by glucocorticoid, long-acting β2-adrenoceptor agonist or both combined.
Project description:RNA sequencing was performed to study the genomic effects of formoterol, a long acting β2-adrenoceptor agonist, alone and in combination with the pro-inflammatory cytokine, TNFα in human primary bronchial epithelial cells, and to compare its effect to forskolin. Our results show that formoterol promoted a profound genomic response alone and on background of an inflammatory stimulus. Moreover, formoterol and forskolin regulated transcriptomes were highly rank order correlated which suggests that formoterol-mediated gene expression changes are cAMP dependent
Project description:Rationale: Asthma is a chronic inflammatory airway disease. The most common medications used for its treatment are β2-agonists and glucocorticosteroids, and one of the primary tissues that these drugs target in the treatment of asthma is the airway smooth muscle. We used RNA-Seq to characterize the human airway smooth muscle (HASM) transcriptome at baseline and under three asthma treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for HASM cells from four white male donors under four treatment conditions: 1) no treatment; 2) treatment with a β2-agonist (i.e. Albuterol, 1μM for 18h); 3) treatment with a glucocorticosteroid (i.e. Dexamethasone (Dex), 1μM for 18h); 4) simultaneous treatment with a β2-agonist and glucocorticoid, and the libraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta mRNA profiles obtained via RNA-Seq for four primary human airway smooth muscle cell lines that were treated with dexamethasone, albuterol, dexamethasone+albuterol or were left untreated.
Project description:Human airway smooth muscle cells were co-cultured with BEAS-2B epithelial cells (or Control). Airway smooth muscle RNA was extracted and sent for Illumina HT-12 micro-array to examine gene expression.
Project description:Airway smooth muscle cells were stimulated with conditioned medium from BEAS-2B cells in the absence (Control) or Inhibition of miR-210.
Project description:Aspergillus fumigatus is an opportunistic fungal pathogen of the respiratory system that may cause invasive infection or an allergic response. Bronchial airway epithelial cells compromise the most abundant cell type of the pulmonary-air interface. Our recent findings suggest loss of Nlrx1 by BEAS-2B airway epithelial cells result in a hyper inflammatory response as well as decreased conidial processing. We challenged wildtype Nlrx1 deficient BEAS-2B cells with viable A. fumigatus AF293 conidia to identify early response differentially expressed genes and pathways between the two cell populations.
