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Open AccessArticle

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

by Nur Aziz 1, Young-Jin Son 2,* and Jae Youl Cho 1,*
1
Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS), Sungkyunkwan University, Suwon 16419, Korea
2
Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1355; https://doi.org/10.3390/ijms19051355
Received: 14 April 2018 / Revised: 30 April 2018 / Accepted: 2 May 2018 / Published: 3 May 2018
(This article belongs to the Section Biochemistry)
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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MDPI and ACS Style

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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