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| Status |
Public on Nov 01, 2018 |
| Title |
MicroRNA-146a and glucocorticoids in inflamed airway epithelial cells |
| Platform organisms |
Macaca mulatta; Homo sapiens; Mus musculus; Rattus norvegicus |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Glucocorticoids are the cornerstone of asthma and other inflammatory disease therapy. Resistance or insensitivity to glucocorticoids presents a substantial and challenging clinical problem. MicroRNAs are emerging as central regulators of inflammation, but it is not clear whether they could augment or attenuate glucocorticoid responses. We aimed to identify microRNAs that regulate cytokine and chemokine expression in airway epithelial cells and whether these miRNAs are subject to the effects of glucocorticoids. MicroRNAomic analyses of primary bronchial epithelial cells and the A549 airway epithelial cell line identified 7 miRNAs that were altered by inflammatory cytokine treatment and 22 that were regulated by glucocorticoids (n=3 for each treatment). miR-146a emerged as a central candidate, whose expression was induced by TNF-alpha and repressed by glucocorticoids. Its role as a candidate in asthmatic inflammation was supported by expression profiling in human asthmatics, which showed that plasma miR-146a expression was elevated in asthma and associated with measures related to worse asthma outcomes, including elevated blood eosinophil counts, higher asthma control questionnaire scores, and need for higher doses of inhaled glucocorticoids. However, transfection of miR-146a in A549 cells treated with TNF-alpha +/- glucocorticoids produced an anti-inflammatory effect and with increased efficacy of glucocorticoids. We propose a model whereby miR-146a is induced by inflammatory conditions as a feedback mechanism to limit inflammation. Glucocorticoids may limit this regulatory pathway by preventing miR-146a expression. Consequently, exogenous administration of miR-146a could be a novel therapeutic strategy to enhance effects of glucocorticoids.
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| Overall design |
Cultures of the human airway epithelial cell line NuLi-1 were treated with control (n=3), dexamethasone (n=3), TNF-alpha (n=3), or dexamathasone plus TNF-alpha (n=3). Total RNA was isolated from the 12 culture samples for evaluation of microRNA expression levels.
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| Contributor(s) |
Ishmael F |
| Citation(s) |
30300399 |
| |
| Submission date |
Oct 02, 2018 |
| Last update date |
Sep 09, 2020 |
| Contact name |
Faoud T Ishmael |
| E-mail(s) |
[email protected]
|
| Phone |
717-531-0003
|
| Organization name |
Penn State College of Medicine
|
| Department |
Division of Pulmonary and Critical Care Medicine
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| Lab |
Section of Allergy and Immunology
|
| Street address |
500 University Dr.
|
| City |
Hershey |
| State/province |
PA |
| ZIP/Postal code |
17033 |
| Country |
USA |
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| Platforms (1) |
| GPL25635 |
ORB MiRBase 19 Multispecies MicroRNA Microarray |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA494399 |
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