MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes

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...

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Main Authors: Tiziana Ada Renzi, Marcello Rubino, Laura Gornati, Cecilia Garlanda, Massimo Locati, Graziella Curtale
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/145305
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author Tiziana Ada Renzi
Marcello Rubino
Laura Gornati
Cecilia Garlanda
Massimo Locati
Graziella Curtale
author_facet Tiziana Ada Renzi
Marcello Rubino
Laura Gornati
Cecilia Garlanda
Massimo Locati
Graziella Curtale
author_sort Tiziana Ada Renzi
collection DOAJ
description 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.
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institution Kabale University
issn 0962-9351
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language English
publishDate 2015-01-01
publisher Wiley
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series Mediators of Inflammation
spelling doaj-art-76d3236c976a45f1a763d9900dff06152025-08-20T03:35:15ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/145305145305MiR-146b Mediates Endotoxin Tolerance in Human PhagocytesTiziana Ada Renzi0Marcello Rubino1Laura Gornati2Cecilia Garlanda3Massimo Locati4Graziella Curtale5Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, ItalyHumanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, ItalyA 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.http://dx.doi.org/10.1155/2015/145305
spellingShingle Tiziana Ada Renzi
Marcello Rubino
Laura Gornati
Cecilia Garlanda
Massimo Locati
Graziella Curtale
MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
Mediators of Inflammation
title MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
title_full MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
title_fullStr MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
title_full_unstemmed MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
title_short MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes
title_sort mir 146b mediates endotoxin tolerance in human phagocytes
url http://dx.doi.org/10.1155/2015/145305
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