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Open AccessArticle

Regulation of 8-Hydroxydaidzein in IRF3-Mediated Gene Expression in LPS-Stimulated Murine Macrophages

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
Basic Research & Innovation Division, R&D Center, AmorePacific Corporation, Yongin 17074, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(2), 238;
Received: 31 October 2019 / Revised: 17 January 2020 / Accepted: 26 January 2020 / Published: 4 February 2020
Cytokines and chemokines are transcriptionally regulated by inflammatory transcription factors such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor (IRF)-3. A daidzein derivative compound, 8-hydroxydaidzein (8-HD), isolated from soy products, has recently gained attention due to various pharmacological benefits, including anti-inflammatory activities. However, regulation of the inflammatory signaling mechanism for 8-HD is still poorly understood, particularly with respect to the IRF-3 signaling pathway. In this study, we explored the molecular mechanism of 8-HD in regulating inflammatory processes, with a focus on the IRF-3 signaling pathway using a lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid [Poly (I:C)] stimulated murine macrophage cell line (RAW264.7). The 8-HD downregulated the mRNA expression level of IRF-3-dependent genes by inhibiting phosphorylation of the IRF-3 transcription factor. The inhibitory mechanism of 8-HD in the IRF-3 signaling pathway was shown to inhibit the kinase activity of IKKε to phosphorylate IRF-3. This compound can also interfere with the TRIF-mediated complex formation composed of TRAF3, TANK, and IKKε leading to downregulation of AKT phosphorylation and reduction of IRF-3 activation, resulted in inhibition of IRF-3-dependent expression of genes including IFN-β, C-X-C motif chemokine 10 (CXCL10), and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). Therefore, these results strongly suggest that 8-HD can act as a promising compound with the regulatory function of IRF-3-mediated inflammatory responses. View Full-Text
Keywords: 8-Hydroxydaidzein; IRF-3; TRAF3; IKKε; inflammation 8-Hydroxydaidzein; IRF-3; TRAF3; IKKε; inflammation
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Aziz, N.; Kang, Y.-G.; Kim, Y.-J.; Park, W.-S.; Jeong, D.; Lee, J.; Kim, D.; Cho, J.Y. Regulation of 8-Hydroxydaidzein in IRF3-Mediated Gene Expression in LPS-Stimulated Murine Macrophages. Biomolecules 2020, 10, 238.

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