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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126981 | GEO | 2019/05/01

REPOSITORIES: GEO

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Project description:BackgroundHexavalent chromium [Cr(VI)] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated.Methods/resultsWe established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI) followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated) that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI) transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI) transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated in all Cr(VI) transformed cells, while genes associated with the interaction between cells and their extracellular matrices were down-regulated. Additionally, expression of genes involved in cell proliferation and apoptosis were also changed.ConclusionThis study is the first to report gene expression profiling of Cr(VI) transformed cells. The gene expression changes across individual chromate exposed clones were remarkably similar to each other but differed significantly from the gene expression found in anchorage-independent clones that arose spontaneously. Our analysis identified many novel gene expression changes that may contribute to chromate induced cell transformation, and collectively this type of information will provide a better understanding of the mechanism underlying chromate carcinogenicity.

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

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