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miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY

The human toll-like receptor 4 (TLR4) pathway is activated in response to lipopolysaccharide (LPS), and subsequent signal transductions lead to the production of cytokines such as tumor necrosis factor-α (TNF-α) by innate immune cells. Defects in innate immune response may contribute to the overprod...

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Autores principales: Nahid, Md A., Pauley, Kaleb M., Satoh, Minoru, Chan, Edward K. L.
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787321/
https://www.ncbi.nlm.nih.gov/pubmed/19840932
http://dx.doi.org/10.1074/jbc.M109.056317
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author Nahid, Md A.
Pauley, Kaleb M.
Satoh, Minoru
Chan, Edward K. L.
author_facet Nahid, Md A.
Pauley, Kaleb M.
Satoh, Minoru
Chan, Edward K. L.
author_sort Nahid, Md A.
collection PubMed
description The human toll-like receptor 4 (TLR4) pathway is activated in response to lipopolysaccharide (LPS), and subsequent signal transductions lead to the production of cytokines such as tumor necrosis factor-α (TNF-α) by innate immune cells. Defects in innate immune response may contribute to the overproduction of TNF-α leading to systemic inflammation and diseases. Thus, the innate immune response needs to be tightly regulated by elaborate mechanisms to control its onset and termination. LPS tolerance is a state of hyporesponsiveness to subsequent LPS challenge and is achieved by monocytic cells after prolonged exposure to LPS. In this report, kinetics of endotoxin-responsive microRNAs expression analysis revealed a unique pattern of gradual increase for miR-146a starting 4 h after LPS stimulation in THP-1 cells and continued up to 35-fold over 24 h. Conversely, TNF-α increased up to 4 h and then decreased gradually implicating a negative correlation with miR-146a progression. The characteristic up-regulation of miR-146a toward subsequent LPS challenge in THP-1 cells was studied. Strikingly, microRNA expression analysis during the tolerized state of THP-1 cells showed only miR-146a overexpression suggesting its important role in LPS tolerance. In addition, LPS tolerance was dependent on a LPS-priming dose and associated miR-146a up-regulation. LPS-tolerized cells were observed to regain responsiveness in TNF-α production 22 h after LPS removal correlating with a decrease in miR-146a level. Transfection of miR-146a into THP-1 cells mimicked LPS priming, whereas transfection of miR-146a inhibitor largely abolished LPS tolerance. Thus our studies demonstrated that miR-146a is critical for the in vitro monocytic cell-based endotoxin tolerance.
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spelling pubmed-27873212009-12-04 miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY Nahid, Md A. Pauley, Kaleb M. Satoh, Minoru Chan, Edward K. L. J Biol Chem RNA-Mediated Regulation and Noncoding RNAs The human toll-like receptor 4 (TLR4) pathway is activated in response to lipopolysaccharide (LPS), and subsequent signal transductions lead to the production of cytokines such as tumor necrosis factor-α (TNF-α) by innate immune cells. Defects in innate immune response may contribute to the overproduction of TNF-α leading to systemic inflammation and diseases. Thus, the innate immune response needs to be tightly regulated by elaborate mechanisms to control its onset and termination. LPS tolerance is a state of hyporesponsiveness to subsequent LPS challenge and is achieved by monocytic cells after prolonged exposure to LPS. In this report, kinetics of endotoxin-responsive microRNAs expression analysis revealed a unique pattern of gradual increase for miR-146a starting 4 h after LPS stimulation in THP-1 cells and continued up to 35-fold over 24 h. Conversely, TNF-α increased up to 4 h and then decreased gradually implicating a negative correlation with miR-146a progression. The characteristic up-regulation of miR-146a toward subsequent LPS challenge in THP-1 cells was studied. Strikingly, microRNA expression analysis during the tolerized state of THP-1 cells showed only miR-146a overexpression suggesting its important role in LPS tolerance. In addition, LPS tolerance was dependent on a LPS-priming dose and associated miR-146a up-regulation. LPS-tolerized cells were observed to regain responsiveness in TNF-α production 22 h after LPS removal correlating with a decrease in miR-146a level. Transfection of miR-146a into THP-1 cells mimicked LPS priming, whereas transfection of miR-146a inhibitor largely abolished LPS tolerance. Thus our studies demonstrated that miR-146a is critical for the in vitro monocytic cell-based endotoxin tolerance. American Society for Biochemistry and Molecular Biology 2009-12-11 2009-10-19 /pmc/articles/PMC2787321/ /pubmed/19840932 http://dx.doi.org/10.1074/jbc.M109.056317 Text en © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle RNA-Mediated Regulation and Noncoding RNAs
Nahid, Md A.
Pauley, Kaleb M.
Satoh, Minoru
Chan, Edward K. L.
miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title_full miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title_fullStr miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title_full_unstemmed miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title_short miR-146a Is Critical for Endotoxin-induced Tolerance: IMPLICATION IN INNATE IMMUNITY
title_sort mir-146a is critical for endotoxin-induced tolerance: implication in innate immunity
topic RNA-Mediated Regulation and Noncoding RNAs
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787321/
https://www.ncbi.nlm.nih.gov/pubmed/19840932
http://dx.doi.org/10.1074/jbc.M109.056317
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