title: A nuclear factor-κB signaling pathway via protein kinase C δ regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells.
abstract: Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma, and severe lower respiratory tract disease in infants and young children. The airway epithelium, which has a well-developed barrier regulated by tight junctions, is the first line of defense during respiratory virus infection. In upper airway human nasal epithelial cells (HNECs), however, the primary site of RSV infection, the mechanisms of replication and budding of RSV, and the epithelial cell responses, including the tight junctional barrier, remain unknown. To investigate the detailed mechanisms of replication and budding of RSV in HNECs and the epithelial cell responses, we established an RSV-infected model using human telomerase reverse transcriptase--transfected HNECs. We first found that the expression and barrier function of tight junction molecules claudin-4 and occludin were markedly induced together with production of proinflammatory cytokines interleukin 8 and tumor necrosis factor-α in HNECs after RSV infection, and the induction of tight junction molecules possibly contributed to budding of RSV. Furthermore, the replication and budding of RSV and the epithelial cell responses in HNECs were regulated via a protein kinase C δ/hypoxia-inducible factor-1α/nuclear factor-κB pathway. The control of this pathway in HNECs may be useful not only for prevention of replication and budding of RSV, but also in therapy for RSV-induced respiratory pathogenesis.
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Ogasawara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohkuni
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Obata
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Jun
authors.initials: J
authors.lastname: Fuchimoto
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D062506:Claudin-4; D057167:Claudins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology / Q000821:virology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D051745:Protein Kinase C-delta