title: Interferon (IFN)-induced protein 35 (IFI35) negatively regulates IFN-β-phosphorylated STAT1-RIG-I-CXCL10/CCL5 axis in U373MG astrocytoma cells treated with polyinosinic-polycytidylic acid.
abstract: Interferon (IFN)-stimulated genes (ISGs) exert multiple functions in immune system. IFN-induced protein 35 (IFI35) is a member of ISGs, and has been suggested to regulate innate immune reaction. However, the physiological functions and pathological roles of IFI35 in the central nervous system are not characterized well. In the present study, we found that the expression of IFI35 was induced by a Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid (poly IC) in U373MG human astrocytoma cells. Knockdown of IFI35 using RNA interference resulted in increased expression of IFN-β, phosphorylated STAT1 (P-STAT1), retinoic acid-inducible gene-I (RIG-I), CXCL10 and CCL5 induced by poly IC. Poly IC-induced expression of CXCL10 and CCL5 was decreased by knockdown of RIG-I. These results suggest that IFI35 may negatively regulate the TLR3-IFN-β-P-STAT1-RIG-I-CXCL10/CCL5 axis in U373MG cells, and IFI35 may play a role at least partially in the regulation of innate immune reactions in astrocytes.
authors.affiliation: Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Shirai
authors.affiliation: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Vascular Biology, 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, 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, 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, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of School Health Science, Faculty of Education, Hirosaki University, 1 Bunkyo-cho, Hirosaki 036-8560, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Vascular Biology, 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
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology*; D001254:Astrocytoma / Q000276:immunology; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D016899:Interferon-beta / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; C085378:IFI35 protein, human; D007369:Interferon Inducers; D047908:Intracellular Signaling Peptides and Proteins; C437968:PLAAT4 protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C
keywords: Astrocytes; Chemokine; IFI35; IFN; RIG-I; TLR3