A nuclear factor-kappa B signaling pathway via protein kinase C delta regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells

作者：Masaki Tomoyuki; Kojima Takashi^*; Okabayashi Tamaki; Ogasawara Noriko; Ohkuni Tsuyoshi; Obata Kazufumi; Takasawa Akira; Murata Masaki; Tanaka Satoshi; Hirakawa Satoshi; Fuchimoto Jun; Ninomiya Takafumi; Fujii Nobuhiro; Tsutsumi Hiroyuki; Himi Tetsuo; Sawada Norimasa

来源：Molecular Biology of the Cell, 2011, 22(13): 2144-2156.

DOI：10.1091/mbc.E10-11-0875

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-alpha 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 delta/hypoxia-inducible factor-1 alpha/nuclear factor-kappa B 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.

• 出版日期2011-7-1