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Int. J. Mol. Sci. 2018, 19(5), 1355;

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

Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS), Sungkyunkwan University, Suwon 16419, Korea
Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea
Authors to whom correspondence should be addressed.
Received: 14 April 2018 / Revised: 30 April 2018 / Accepted: 2 May 2018 / Published: 3 May 2018
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: thymoquinone; type I interferons; IRF-3; TBK1; inflammation thymoquinone; type I interferons; IRF-3; TBK1; inflammation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Aziz, N.; Son, Y.-J.; Cho, J.Y. Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1. Int. J. Mol. Sci. 2018, 19, 1355.

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