title: Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic-polycytidylic acid in U373MG human astrocytoma cells.
abstract: Although iron is essential in physiological processes, accumulation of iron in central nervous system is associated with various neurological diseases including Alzheimer's disease and Parkinson's disease. Innate immune reactions are involved in the pathogenesis of those diseases, but roles of iron in innate immunity are not known well. In the present study, pretreatment of U373MG human astrocytoma cells with an iron chelator desferrioxamine (DFX) inhibited the expression of CXCL10 induced by a Toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (poly IC). Induction of interferon-β (IFN-β) was not affected, but phosphorylation of signal transducer and transcription 1 (STAT1) was decreased by DFX. We have previously reported that various IFN-stimulated genes (ISGs) are involved in CXCL10 induction by poly IC. Pretreatment with DFX also decreased the expression of these ISGs. Pretreatment of cells with FeSO4 counteracted inhibitory effects of DFX on ISG56, retinoic acid-inducible gene-I (RIG-I), CXCL10 and phosphorylation of STAT1. These results suggest that iron may positively regulate STAT1 phosphorylation and following signaling to express ISG56, RIG-I and CXCL10 in U373MG cells treated with poly IC. Iron may contribute to innate immune and inflammatory reactions elicited by the TLR3 signaling in astrocytes, and may play an important role in neuroinflammatory diseases.
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@cc.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: Nina
authors.initials: N
authors.lastname: Sakashita
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: Yasuaki
authors.initials: Y
authors.lastname: Mushiga
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: Liang
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 Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Dentistry and Oral Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Furudate
authors.affiliation: Department of Gastroenterology and Hematology, 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: D001254:Astrocytoma / Q000473:pathology; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007369:Interferon Inducers; D007502:Iron Chelating Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D042461:Vascular Endothelial Growth Factor A; D003676:Deferoxamine; D011070:Poly I-C
keywords: CXCL10; DFX; FeSO(4); STAT1; TLR3; U373MG cells