Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
In: International Journal of Molecular Sciences, Jg. 19 (2018-05-01), Heft 5, S. 1355
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Zugriff:
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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Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1
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Autor/in / Beteiligte Person: | Aziz, Nur ; Son, Young-Jin ; Jae Youl Cho |
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Zeitschrift: | International Journal of Molecular Sciences, Jg. 19 (2018-05-01), Heft 5, S. 1355 |
Veröffentlichung: | MDPI AG, 2018 |
Medientyp: | academicJournal |
ISSN: | 1422-0067 (print) |
DOI: | 10.3390/ijms19051355 |
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