Document Detail

miR-146a regulates mechanotransduction and pressure-induced inflammation in small airway epithelium.
MedLine Citation:
PMID:  22593544     Owner:  NLM     Status:  MEDLINE    
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.
Yan Huang; Melissa Crawford; Natalia Higuita-Castro; Patrick Nana-Sinkam; Samir N Ghadiali
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Publication Detail:
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:
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:
Created Date:  2012-08-01     Completed Date:  2012-10-16     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3351-64     Citation Subset:  IM    
Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
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MeSH Terms
Cells, Cultured
Cytokines / secretion*
Epithelial Cells / drug effects*
Inflammation / etiology*
Interleukin-1 Receptor-Associated Kinases / drug effects,  metabolism
Lung / physiopathology*
Mechanotransduction, Cellular / drug effects
MicroRNAs / biosynthesis,  physiology*
NF-kappa B / pharmacology
TNF Receptor-Associated Factor 6 / drug effects,  metabolism
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
CA150297-01/CA/NCI NIH HHS
Reg. No./Substance:
0/Cytokines; 0/MIRN146 microRNA, human; 0/MicroRNAs; 0/NF-kappa B; 0/TNF Receptor-Associated Factor 6; 0/Tumor Necrosis Factor-alpha; EC protein, human; EC Receptor-Associated Kinases

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