title: Interferon-stimulated gene (ISG) 60, as well as ISG56 and ISG54, positively regulates TLR3/IFN-β/STAT1 axis in U373MG human astrocytoma cells.
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.
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: timaizum@hirosaki-u.ac.jp.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kawaguchi
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki 036-8560, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D014157:Transcription Factors; D016899:Interferon-beta; D011070:Poly I-C
keywords: CXCL10; ISG54; ISG56; ISG60; STAT1; TLR3