title: Induction of interferon-induced transmembrane protein 3 gene expression by lipopolysaccharide in astrocytes.
abstract: Astrocytes are important modulators of the immune and inflammatory reactions in the central nervous system. We have recently demonstrated the role of interferon-induced transmembrane protein 3 (IFITM3) in long-lasting neuronal impairments in mice following neonatal immune challenge by injections of the double-stranded RNA analog polyriboinosinic polyribocytidylic acid. Here, we show that IFITM3 is induced after lipopolysaccharide (LPS) treatment in cultured astrocytes. The induction of IFITM3 by LPS was completely suppressed by the addition of anti-interferon-β (IFN-β) antibody. In addition, neutralization of tumor necrosis factor-α (TNF-α) with its antibody partially inhibited the induction of IFITM3, suggesting that LPS induces IFITM3 through autocrine secretion of IFN-β and TNF-α. Furthermore, experiments using pharmacological inhibitors suggest that LPS induces IFITM3 through activation of TANK-binding kinase 1, p38 mitogen-activated protein kinase, and nuclear factor-κB pathways. Together, these findings may provide new insight into the role of IFITM3 in the pathogenesis of neurodevelopmental diseases associated with immune activation.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan; Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ibi
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan; Department of Regional Pharmaceutical Care and Sciences, Faculty of Pharmacy, Meijo University, Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan. Electronic address: kyamada@med.nagoya-u.ac.jp.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D016899:Interferon-beta / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C462181:fragilis protein, mouse; D016899:Interferon-beta; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Astrocyte; IFITM3; Lipopolysaccharide; Pattern-recognition receptor