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Role of microRNA‐146a in regulating mechanically induced inflammation in human lung epithelial cells
Author(s) -
Ghadiali Samir,
Huang Yan,
Crawford Melissa,
NanaSinkam Patrick
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.663.2
Subject(s) - inflammation , microrna , secretion , mechanotransduction , tumor necrosis factor alpha , lung , microbiology and biotechnology , cytokine , chemistry , gene knockdown , signal transduction , biology , immunology , medicine , apoptosis , gene , biochemistry
Although lung epithelial cells can transduce mechanical forces into inflammatory signaling, the mechanisms responsible for regulating this mechanotransduction processes are not known. Our laboratory is investigating the novel hypothesis that microRNAs (miRNAs) may be important regulators of mechanically induced inflammation. In this study we demonstrate that transmural pressures can activate NF‐κB signaling pathways and alter miRNA expression profiles. We also demonstrate that miR‐146a regulates mechanically induced inflammation. Primary human small airway epithelial cells (HAEpC) were exposed to either oscillatory pressure (0–20 cm H2O, 0.2 Hz), 30 ng/mL TNF‐α or both TNF‐α and oscillatory pressure. The Nanostring nCounter system was used to profile miRNA expression and results were validated via qRT‐PCR. 12h of exposure to either TNF‐α or oscillatory pressure induced a 2x increase in miR‐146a expression while exposure to both TNF‐α and pressure resulted in slightly higher miR‐146a expression. Similarly, exposure to TNF‐α and pressure showed synergistic effects on cytokine (IL‐6 and IL‐8) secretion. Knocking down miR‐146a resulted in increased IL‐6 secretion while overexpression resulted in decreased IL‐6 secretion. We conclude that miR‐146a is a mechano‐sensitive micro‐RNA which regulates mechanically induced inflammation in lung epithelia. Supported by NSF 0852417.