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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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84880 | GEO | 2016/07/27

SECONDARY ACCESSION(S): PRJNA335419

REPOSITORIES: GEO

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A comparison of GS-5759, a bifunctional Î²2-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 Î²2-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 Î²2-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).

2016-07-27 | E-GEOD-84880 | biostudies-arrayexpress

An analysis of the effect of indacaterol and GSK 256066 alone and in combination on gene expression changes in the BEAS-2B human airway epithelial cell line.

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.

2017-11-09 | GSE106710 | GEO

Homo sapiens

Project description: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

| PRJNA335419 | ENA

Gene expression analysis of human bronchial airway epithelial BEAS-2B cells stimulated by glucocorticoid, long-acting β2-adrenoceptor agonist or both combined.

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.

2019-08-01 | GSE115830 | GEO

Effect of Salmeterol and Roflumilast N-oxide (RNO) alone and in combination on gene expression changes in BEAS-2B human airway epithelial cell line

Project description:RNA-sequencing was performed to study the effect of phosphodiesterase 4 inhibition by Roflumilast N-oxide (RNO) on gene expression changes produced by sub-maximal concentrations of the long acting β2-adrenoceptor agonist, Salmeterol. Our results indicate that RNO enhanced the expression of all salmeterol-regulated genes, but the degree of enhancement varied between genes due to the difference in their sensitivities to salmeterol.

2019-05-01 | GSE126981 | GEO

Olanzapine suppresses mPFC-norepinephrine releasing to alleviate CLOCK-induced cancer stemness under chronic stress

Project description:We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ reversed chronic stress-enhanced lung tumorigenesis and anxiety-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing. To investigate the mechanism of NE in cancer stemness we performed RNA-seq of the NCI-H1299 cells under NE treatment and found that NE activated β2-adrenoceptor (ADRB2)-mediated cAMP-PKA-CREB pathway to transactivate CLOCK that further sustains cancer stemness.

2024-08-02 | GSE268860 | GEO

Effect of formoterol and tumor necrosis factor (TNFα) alone and in combination on gene expression changes in human primary bronchial epithelial cells: a comparison with forskolin treatment

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

2022-06-28 | GSE202436 | GEO

Expression profiling of skeletal muscle following acute β2-adrenergic stimulation

Project description:Systemic administration of β-adrenoceptor (β-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1–3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic acute administration of the β2-AR agonist formoterol. Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using 46K Illumina(R) Sentrix BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress.

2009-04-24 | GSE15793 | GEO

Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis

Project description:G protein-coupled receptors (GPCRs) are well known to signal via cyclic AMP (cAMP) production at the plasma membrane, but it is now clear that various GPCRs also signal after internalization. Apart from its temporal impact through prolonging the cellular response, we wondered if the endosome-initiated signal encodes any discrete spatial information. Using the beta2-adrenoceptor (β2-AR) as a model, we show that endocytosis is required for the full repertoire of downstream cAMP-dependent transcriptional control. Next, we describe an orthogonal optogenetic approach to definitively establish that the location of cAMP production is indeed the critical variable determining the transcriptional response. Finally, our results suggest that this spatial encoding scheme helps cells functionally discriminate chemically distinct β2-AR ligands according to differences in their ability to promote receptor endocytosis. These findings reveal a discrete principle for achieving cellular signalling specificity, based on endosome-mediated spatial encoding of intracellular second messenger production and 'location aware' downstream transcriptional control.

2014-11-01 | GSE57274 | GEO

Gene expression analysis of normal primary human bronchial epithelial cells (pHBEC) stimulated by glucocorticoid, long-acting β2-adrenoceptor agonist or both combined.

Project description:In 2019, the Global Initiative for Asthma treatment guidelines were updated to recommend that inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy should be a first-in-line treatment option for asthma. Although clinically superior to ICS, mechanisms underlying the efficacy of this combination therapy remain unclear. We hypothesised the existence of transcriptomic interactions, an effect that was tested in primary human bronchial epithelial cells (pHBECs) using formoterol and budesonide as representative LABA and ICS, respectively. To investigate the gene expression changes by each condition, transcriptomic analysis was performed on RNA extracted from pHBECs treated with budesonide, formoterol, or both combined.

2020-11-20 | GSE161805 | GEO

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