Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic–polycytidylic acid in U373MG human astrocytoma cells. (May 2015)

• Record Type: Journal Article
• Authors: Imaizumi, Tadaatsu; Sakashita, Nina; Mushiga, Yasuaki; Yoshida, Hidemi; Hayakari, Ryo; Xing, Fei; Wang, Liang; Matsumiya, Tomoh; Tanji, Kunikazu; Chiba, Yuki; Furudate, Ken; Kawaguchi, Shogo; Murakami, Manabu; Tanaka, Hiroshi
• Is Part Of: Neuroscience research. Volume 94(2015:May)
• Page Start: 10
• Page End: 16
• Publication Date: 2015-05
• Subjects: DFX desferrioxamine -- IFN interferon -- ISG IFN-stimulated gene -- MDA5 melanoma differentiation-associated gene 5 -- RIG-I retinoic acid-inducible gene-I -- poly IC polyinosinic–polycytidylic acid -- TLR3 Toll-like receptor 3; DFX -- FeSO4 -- TLR3 -- STAT1 -- CXCL10 -- U373MG cells; 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.2015.01.001
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Desferrioxamine, an iron chelator, inhibited CXCL10 expression induced by poly IC in U373MG human astrocytoma cells. Phosphorylation of STAT1 elicited by poly IC was decreased by desferrioxamine. Induction of ISGs including ISG56, ISG54, RIG-I and MDA was decreased by desferrioxamine. Iron may positively regulate STAT1 phosphorylation and following expression of ISGs and CXCL10 induced by poly IC. This reaction regulated by iron may play a role in neuroinflammatory diseases. 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.