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Mediators of Inflammation
Volume 2015 (2015), Article ID 145305, 10 pages
http://dx.doi.org/10.1155/2015/145305
Research Article

MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes

1Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
2Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy
3Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA

Received 11 March 2015; Revised 26 June 2015; Accepted 12 July 2015

Academic Editor: Barbro N. Melgert

Copyright © 2015 Tiziana Ada Renzi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A proper regulation of the innate immune response is fundamental to keep the immune system in check and avoid a chronic status of inflammation. As they act as negative modulators of TLR signaling pathways, miRNAs have been recently involved in the control of the inflammatory response. However, their role in the context of endotoxin tolerance is just beginning to be explored. We here show that miR-146b is upregulated in human monocytes tolerized by LPS, IL-10, or TGFβ priming and demonstrate that its transcription is driven by STAT3 and RUNX3, key factors downstream of IL-10 and TGFβ signaling. Our study also found that IFNγ, known to revert LPS tolerant state, inhibits miR-146b expression. Finally, we provide evidence that miR-146b levels have a profound effect on the tolerant state, thus candidating miR-146b as a molecular mediator of endotoxin tolerance.