| miR-146a regulates mechanotransduction and pressure-induced inflammation in small airway epithelium. | |
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MedLine Citation:
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PMID: 22593544 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mechanical ventilation generates biophysical forces, including high transmural pressures, which exacerbate lung inflammation. This study sought to determine whether microRNAs (miRNAs) respond to this mechanical force and play a role in regulating mechanically induced inflammation. Primary human small airway epithelial cells (HSAEpCs) were exposed to 12 h of oscillatory pressure and/or the proinflammatory cytokine TNF-α. Experiments were also conducted after manipulating miRNA expression and silencing the transcription factor NF-κB or toll-like receptor proteins IRAK1 and TRAF6. NF-κB activation, IL-6/IL-8/IL-1β cytokine secretion, miRNA expression, and IRAK1/TRAF6 protein levels were monitored. A total of 12 h of oscillatory pressure and TNF-α resulted in a 5- to 7-fold increase in IL-6/IL-8 cytokine secretion, and oscillatory pressure also resulted in a time-dependent increase in IL-6/IL-8/IL-1β cytokine secretion. Pressure and TNF-α also resulted in distinct patterns of miRNA expression, with miR-146a being the most deregulated miRNA. Manipulating miR-146a expression altered pressure-induced cytokine secretion. Silencing of IRAK1 or TRAF6, confirmed targets of miR-146a, resulted in a 3-fold decrease in pressure-induced cytokine secretion. Cotransfection experiments demonstrate that miR-146a's regulation of pressure-induced cytokine secretion depends on its targeting of both IRAK1 and TRAF6. MiR-146a is a mechanosensitive miRNA that is rapidly up-regulated by oscillatory pressure and plays an important role in regulating mechanically induced inflammation in lung epithelia. |
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Authors:
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Yan Huang; Melissa Crawford; Natalia Higuita-Castro; Patrick Nana-Sinkam; Samir N Ghadiali |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-05-16 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 26 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-08-01 Completed Date: 2012-10-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 3351-64 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Cytokines / secretion* Epithelial Cells / drug effects* Humans Inflammation / etiology* Interleukin-1 Receptor-Associated Kinases / drug effects, metabolism Lung / physiopathology* Mechanotransduction, Cellular / drug effects MicroRNAs / biosynthesis, physiology* NF-kappa B / pharmacology Pressure TNF Receptor-Associated Factor 6 / drug effects, metabolism Tumor Necrosis Factor-alpha / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA150297-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/MIRN146 microRNA, human; 0/MicroRNAs; 0/NF-kappa B; 0/TNF Receptor-Associated Factor 6; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.1/IRAK1 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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