Dataset Information

MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy.

ABSTRACT:

Background

Asthma is a common disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and chronic inflammation, which is commonly treated using corticosteroids such as budesonide. MicroRNAs (miRNAs) are a recently identified family of non-protein encoding genes that regulate protein translation by a mechanism entitled RNA interference. Previous studies have shown lung-specific miRNA expression profiles, although their importance in regulating gene expression is unresolved. We determined whether miRNA expression was differentially expressed in mild asthma and the effect of corticosteroid treatment.

Methodology/principal findings

We have examined changes in miRNA using a highly sensitive RT-PCR based approach to measure the expression of 227 miRNAs in airway biopsies obtained from normal and mild asthmatic patients. We have also determined whether the anti-inflammatory action of corticosteroids are mediated through miRNAs by determining the profile of miRNA expression in mild asthmatics, before and following 1 month twice daily treatment with inhaled budesonide. Furthermore, we have analysed the expression of miRNAs from individual cell populations from the airway and lung. We found no significant difference in the expression of 227 miRNAs in the airway biopsies obtained from normal and mild asthmatic patients. In addition, despite improved lung function, we found no significant difference in the miRNA expression following one month treatment with the corticosteroid, budesonide. However, analysis of bronchial and alveolar epithelial cells, airway smooth muscle cells, alveolar macrophages and lung fibroblasts demonstrate a miRNA expression profile that is specific to individual cell types and demonstrates the complex cellular heterogeneity within whole tissue samples.

Conclusions

Changes in miRNA expression do not appear to be involved in the development of a mild asthmatic phenotype or in the anti-inflammatory action of the corticosteroid budesonide.

SUBMITTER: Williams AE

PROVIDER: S-EPMC2690402 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Publications

MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy.

Williams Andrew E AE Larner-Svensson Hanna H Perry Mark M MM Campbell Gaynor A GA Herrick Sarah E SE Adcock Ian M IM Erjefalt Jonas S JS Chung Kian Fan KF Lindsay Mark A MA

PloS one 20090612 6

<h4>Background</h4>Asthma is a common disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and chronic inflammation, which is commonly treated using corticosteroids such as budesonide. MicroRNAs (miRNAs) are a recently identified family of non-protein encoding genes that regulate protein translation by a mechanism entitled RNA interference. Previous studies have shown lung-specific miRNA expression profiles, although their importance in regulating gene expressio ...[more]

PMID: 19521514

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Project description:Background and purposeInhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.Experimental approachBronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.Key resultsCompared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.Conclusions and implicationsExpression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.

Dataset Information

MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy.

Background

Methodology/principal findings

Conclusions

Publications

MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy.

Similar Datasets

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