Interferon-stimulated gene (ISG) 60, as well as ISG56 and ISG54, positively regulates TLR3/IFN-β/STAT1 axis in U373MG human astrocytoma cells. (April 2016)

• Record Type: Journal Article
• Authors: Imaizumi, Tadaatsu; Yoshida, Hidemi; Hayakari, Ryo; Xing, Fei; Wang, Lian; Matsumiya, Tomoh; Tanji, Kunikazu; Kawaguchi, Shogo; Murakami, Manabu; Tanaka, Hiroshi
• Is Part Of: Neuroscience research. Volume 105(2016:Apr.)
• Page Start: 35
• Page End: 41
• Publication Date: 2016-04
• Subjects: IFN interferon -- IFN IFN induced proteins with tetratricopeptide repeats -- ISG IFN-stimulated gene -- poly IC polyinosinic–polycytidylic acid -- STAT1 signal transducers and activators of transcription -- TLR Toll-like receptor; TLR3 -- ISG60 -- ISG56 -- ISG54 -- STAT1 -- CXCL10; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2015.09.002
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Poly IC induced ISG60 in U373MG cells. TLR3, IFN-β, ISG56 and ISG54 are involved in this reaction. ISG60, ISG54 and ISG56 positively regulate the level of phosphorylated STAT1. A positive feedback loop is created by phosphorylated STAT1 and these ISGs. ISG60 regulates CXCL10 expression induced by poly IC. Abstract: Treatment of cells with interferons (IFNs) induces the phosphorylation of signal transducer and activator of transcription 1 (STAT1), leading to the expression of hundreds of IFN-stimulated genes (ISGs). ISGs exert various antiviral and pro-inflammatory reactions. We have previously reported that ISG56 and ISG54 are induced by polyinosinic–polycytidylic acid (poly IC), an authentic agonist for Toll-like receptor 3 (TLR3), in U373MG human astrocytoma cells. ISG56 and ISG54 are also named as IFN-induced proteins with tetratricopeptide repeats (IFIT) 1 and IFIT2, respectively. In the present study, we demonstrated that poly IC induces the expression of ISG60, also named as IFIT3, in U373MG cells. RNA interference experiments showed that the induction of ISG60 by poly IC was mediated by TLR3, IFN-β, ISG56 and ISG54, whereas ISG60 is involved in poly IC-induced expression of ISG56, ISG54 and a chemokine CXCL10. The level of phosphorylated STAT1 was enhanced by poly IC, and it was inhibited by knockdown of ISG56, ISG54 or ISG60. These results suggest that there is a positive feedback loop between phosphorylated STAT1 and these ISGs.