The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway

  • Kim, Yong (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kim, Han Gyung (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Han, Sang Yun (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Jeong, Deok (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yang, Woo Seok (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kim, Jung-Il (Department of Information Statistics, Kangwon National University) ;
  • Kim, Ji Hye (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yi, Young-Su (Department of Pharmaceutical Engineering, Cheongju University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2017.04.26
  • Accepted : 2017.06.09
  • Published : 2017.09.01
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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 $(IFN)-{\beta}$ 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-${\beta}$ (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, $IFN-{\beta}$, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.

Keywords

References

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