Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway.
10.4196/kjpp.2017.21.5.547
- Author:
Yong KIM
1
;
Han Gyung KIM
;
Sang Yun HAN
;
Deok JEONG
;
Woo Seok YANG
;
Jung Il KIM
;
Ji Hye KIM
;
Young Su YI
;
Jae Youl CHO
Author Information
1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. kjhmlkjhml@hanmail.net, jaecho@skku.edu
- Publication Type:Original Article
- Keywords:
AKT;
Hydroquinone;
IFN-β;
Inflammation;
IRF-3;
Macrophage
- MeSH:
Benzene;
HEK293 Cells;
Inflammation;
Interferons;
Luciferases;
Macrophages;
Phosphorylation;
Phosphotransferases;
Protein Isoforms;
RNA, Messenger
- From:The Korean Journal of Physiology and Pharmacology
2017;21(5):547-554
- CountryRepublic of Korea
- Language:English
-
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.
