MicroRNA-146a is upregulated by and negatively regulates TLR2 signaling

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Date
2013-04-29
Authors
Quinn, Edel M.
Wang, Jiang Huai
O'Callaghan, Grace
Redmond, H. Paul
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PLOS ONE
Published Version
10.1371/journal.pone.0062232
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Abstract
TLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p,0.001). Restimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not grampositive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p,0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-a production (p,0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IkBa expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsis
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Keywords
TLR signaling , MicroRNAs , Immune response to infection
Citation
Quinn EM, Wang JH, O’Callaghan G, Redmond HP (2013) MicroRNA-146a Is Upregulated by and Negatively Regulates TLR2 Signaling. PLoS ONE 8(4): e62232. doi:10.1371/journal.pone.0062232
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https://hdl.handle.net/10468/1158
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Surgery - Journal Articles
Medicine - Journal Articles
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©2013 Quinn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.