Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway
The Korean Journal of Physiology and Pharmacology
; : 547-554, 2017.
Article
in En
| WPRIM
| ID: wpr-728758
Responsible library:
WPRO
ABSTRACT
Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon (IFN)-β mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK-binding kinase 1 (TBK1). A mechanism study revealed that HQ inhibited IRF-3 phosphorylation induced by lipopolysaccharide (LPS), TRIF, and AKT by suppressing phosphorylation of AKT, an upstream kinase of the IRF-3 signaling pathway. IRF-3 phosphorylation is highly induced by wild-type AKT and poorly induced by an AKT mutant, AKT C310A, which is mutated at an inhibitory target site of HQ. We also showed that HQ inhibited IRF-3 phosphorylation by targeting all three AKT isoforms (AKT1, AKT2, and AKT3) in RAW264.7 cells and suppressed IRF-3-mediated luciferase activities induced by AKT in HEK293 cells. Taken together, these results strongly suggest that HQ inhibits the production of a type I IFN, IFN-β, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Phosphorylation
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Phosphotransferases
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Benzene
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RNA, Messenger
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Interferons
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Protein Isoforms
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HEK293 Cells
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Inflammation
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Luciferases
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Macrophages
Language:
En
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2017
Type:
Article