|
KMID : 0811720170210050547
|
|
Korean Journal of Physiology & Pharmacology
2017 Volume.21 No. 5 p.547 ~ p.554
|
|
|
Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway
|
|
Kim Yong
Kim Han-Gyung
Han Sang-Yun
Jeong Deok
Yang Woo-Seok
Kim Jung-Il
Kim Ji-Hye
Yi Young-Su
Cho Jae-Youl
|
|
|
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.
|
|
|
KEYWORD
|
|
|
AKT, Hydroquinone, IFN-β, Inflammation, IRF-3, Macrophage
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|
|