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

International Journal of Molecular Sciences
Nur AzizJae Youl Cho

Abstract

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 downreg...Continue Reading

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Citations

May 7, 2020·Cancers·Nur AzizAnd Jae Youl Cho
Jun 11, 2019·Frontiers in Immunology·Aleksandra AntonczykHans A R Bluyssen
Oct 14, 2020·Phytotherapy Research : PTR·Mohammad Nazrul IslamMd Jamal Uddin
Aug 11, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Muhammad Fakhar-E-Alam KulyarJiakui Li
Dec 29, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Md Yousuf AliMd Asaduzzaman Khan
Jun 5, 2021·Food & Function·Chandan SarkarMohammad S Mubarak
Jun 11, 2021·International Journal of Biological Macromolecules·Manzar AlamMd Imtaiyaz Hassan
Jul 26, 2021·Drug Discovery Today·Safiya MalikVijay Kumar Kapoor
Oct 13, 2019·Current Medicinal Chemistry·Zakia AkterMd Asaduzzaman Khan
May 7, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yasmina K Mahmoud, Heba M A Abdelrazek

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Methods Mentioned

BETA
PCR
transfection
Assay
electrophoresis

Software Mentioned

VeriFlex
SPSS

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