IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response

Mukhopadhyay, P. et al. (2017) IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response. PLoS ONE, 12(9), e0183987. (doi: 10.1371/journal.pone.0183987) (PMID:28910312) (PMCID:PMC5598939)

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Abstract

Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB). Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0.05). miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05). Notably, IκK-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-α and IL-10 production (P < 0.05), and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of IκK-16 inhibition, miR-155 mimics increased TNF-α production, while miR-155 antagomirs decreased both TNF-α and IL-10 production. These data demonstrate that IκK-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that IκK-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.

Item Type:Articles
Additional Information:Funding: This publication was funded by the John W. Price and Barbara Thruston Atwood Price Trust, by the James and Emmeline Ferguson Research Fellowship Trust, by the Dizney Family Foundation, and by the Mary K. Oxley Foundation.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Galbraith, Dr Norman
Creator Roles:
Galbraith, N.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Supervision, Writing – original draft, Writing – review and editing
Authors: Mukhopadhyay, P., Galbraith, N. J., Burton, J., Ekman, M. B., Kenney, J., Walker, S. P., Manek, S., Bishop, C., Carter, J. V., Gardner, S. A., and Polk, H. C.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Galbraith et al.
First Published:First published in PLoS ONE 12(9):e0183987
Publisher Policy:Reproduced under a Creative Commons licence

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