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Korean J Physiol Pharmacol 2017 Sep; 21(5): 547-554
Yong Kim1, Han Gyung Kim1, Sang Yun Han1, Deok Jeong1, Woo Seok Yang1, Jung-Il Kim 2, Ji Hye Kim1,*, Young-Su Yi3,*, and Jae Youl Cho1,*
Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway
1Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, 2Department of Information Statistics, Kangwon National University, Chucheon24341, 3Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Korea
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