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Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1

Interferon regulatory factor (IRF)-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin (Nigella sativa L.) and is known to regulate immune responses by affe...

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Autores principales: Aziz, Nur, Son, Young-Jin, Cho, Jae Youl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983753/
https://www.ncbi.nlm.nih.gov/pubmed/29751576
http://dx.doi.org/10.3390/ijms19051355
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author Aziz, Nur
Son, Young-Jin
Cho, Jae Youl
author_facet Aziz, Nur
Son, Young-Jin
Cho, Jae Youl
author_sort Aziz, Nur
collection PubMed
description Interferon regulatory factor (IRF)-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin (Nigella sativa L.) and is known to regulate immune responses by affecting transcription factors associated with inflammation, including nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). However, the role of TQ in the IRF-3 signaling pathway has not been elucidated. In this study, we explored the molecular mechanism of TQ-dependent regulation of enzymes in IRF-3 signaling pathways using the lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cell line. TQ decreased mRNA expression of the interferon genes IFN-α and IFN-β in these cells. This inhibition was due to its suppression of the transcriptional activation of IRF-3, as shown by inhibition of IRF-3 PRD (III-I) luciferase activity as well as the phosphorylation pattern of IRF-3 in the immunoblotting experiment. Moreover, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream key enzyme responsible for IRF-3 activation. Taken together, these findings suggest that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would subsequently decrease the production of type I IFN. TQ also regulated IRF-3, one of the inflammatory transcription factors, providing a novel insight into its anti-inflammatory activities.
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spelling pubmed-59837532018-06-05 Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1 Aziz, Nur Son, Young-Jin Cho, Jae Youl Int J Mol Sci Article Interferon regulatory factor (IRF)-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin (Nigella sativa L.) and is known to regulate immune responses by affecting transcription factors associated with inflammation, including nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). However, the role of TQ in the IRF-3 signaling pathway has not been elucidated. In this study, we explored the molecular mechanism of TQ-dependent regulation of enzymes in IRF-3 signaling pathways using the lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cell line. TQ decreased mRNA expression of the interferon genes IFN-α and IFN-β in these cells. This inhibition was due to its suppression of the transcriptional activation of IRF-3, as shown by inhibition of IRF-3 PRD (III-I) luciferase activity as well as the phosphorylation pattern of IRF-3 in the immunoblotting experiment. Moreover, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream key enzyme responsible for IRF-3 activation. Taken together, these findings suggest that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would subsequently decrease the production of type I IFN. TQ also regulated IRF-3, one of the inflammatory transcription factors, providing a novel insight into its anti-inflammatory activities. MDPI 2018-05-03 /pmc/articles/PMC5983753/ /pubmed/29751576 http://dx.doi.org/10.3390/ijms19051355 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aziz, Nur
Son, Young-Jin
Cho, Jae Youl
Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title_full Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title_fullStr Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title_full_unstemmed Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title_short Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
title_sort thymoquinone suppresses irf-3-mediated expression of type i interferons via suppression of tbk1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983753/
https://www.ncbi.nlm.nih.gov/pubmed/29751576
http://dx.doi.org/10.3390/ijms19051355
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