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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-5983753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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