A nuclear factor-κB signaling pathway via protein kinase C δ regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells
| Autor: | Takafumi Ninomiya, Tsuyoshi Ohkuni, Tamaki Okabayashi, Tetsuo Himi, Noriko Ogasawara, Norimasa Sawada, Hiroyuki Tsutsumi, Jun Fuchimoto, Nobuhiro Fujii, Tomoyuki Masaki, Satoshi Hirakawa, Masaki Murata, Takashi Kojima, Satoshi Tanaka, Akira Takasawa, Kazufumi Obata |
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| Rok vydání: | 2011 |
| Předmět: |
viruses
Respiratory Syncytial Virus Infections Biology Virus Replication Occludin Virus Tight Junctions Proinflammatory cytokine Transforming Growth Factor beta1 Humans Interleukin 8 Claudin-4 Molecular Biology Tight junction Tumor Necrosis Factor-alpha Interleukin-8 NF-kappa B Epithelial Cells Articles Cell Biology respiratory system Hypoxia-Inducible Factor 1 alpha Subunit Up-Regulation Cell biology Nasal Mucosa Protein Kinase C-delta Cell Biology of Disease Gene Knockdown Techniques Respiratory Syncytial Virus Human Claudins Respiratory epithelium Tumor necrosis factor alpha Signal transduction Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e10-11-0875 |
| Popis: | We established a respiratory syncytial virus (RSV)-infected model in polarized normal human nasal epithelial cells and found that the replication of RSV and the epithelial cell responses including induction of tight junctions were regulated via a protein kinase C δ/hypoxia-inducible factor-1α/nuclear factor-κβ pathway. The control of this pathway may be useful in therapy for RSV-induced respiratory pathogenesis. 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. |
| Databáze: | OpenAIRE |
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