title: Negative regulation of human astrocytes by interferon (IFN) α in relation to growth inhibition and impaired glucose utilization.
abstract: The present study assessed the direct effects of IFNs on human astrocytes. Human astrocytes were exposed to human recombinant IFNs, and the proliferation of cells was measured. Type I IFN receptor mRNA and protein expression, the phosphoprotein levels of signaling molecules including JNK, ERK1/2, IκB, p38MAPK, Stat3, and the expression of cytokines were determined respectively. In addition, cellular glucose consumption was measured as well as Glut-1 protein and activation of GSK-3β/mTOR signal were determined. The expression of Type I IFN receptor was detected in cultured human astrocytes. 2 IU/ml IFNα2a and IFNα2b significantly decreased the proliferation of human astrocytes respectively, compared to control. IFNβ had no significant effect on the proliferation of the cells. The phosphorylation of JNK stimulated by all IFNs detected was more pronounced and sustained than ERK1/2 and IκB. No effects were observed on the activation of p38MAPK and Stat3. Moreover, Treatment with IFNα, especially with IFNα2b, decreased glucose consumption and stimulated phosphorylation of GSK-3β and mTOR, but decreased the expression of Glut-1. In contrast, IFNβ had no significant effect on either glucose consumption or activation of GSK-3β/mTOR signals. INFα2b significantly decreased the levels of IL-8 whereas the levels of GM-CSF were increased. The present study demonstrates direct inhibitory effects of IFNα on cell proliferation, cell signaling and glucose utilization in human astrocytes.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takikawa
authors.forename: Kei
authors.initials: K
authors.lastname: Sawara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053633:Receptor, Interferon alpha-beta / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; C546842:MTOR protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D005947:Glucose