title: Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells.
abstract: Respiratory syncytial virus (RSV) is an important pathogen of bronchiolitis, asthma, and severe lower respiratory tract disease in infants and young children. Matrix metalloproteinases (MMPs) play key roles in viral infection, inflammation and remodeling of the airway. However, the roles and regulation of MMPs in human nasal epithelial cells (HNECs) after RSV infection remain unclear. To investigate the regulation of MMP induced after RSV infection in HNECs, an RSV-infected model of HNECs in vitro was used. It was found that mRNA of MMP-10 was markedly increased in HNECs after RSV infection, together with induction of mRNAs of MMP-1, -7, -9, and -19. The amount of MMP-10 released from HNECs was also increased in a time-dependent manner after RSV infection as was that of chemokine RANTES. The upregulation of MMP-10 in HNECs after RSV infection was prevented by inhibitors of NF-κB and pan-PKC with inhibition of RSV replication, whereas it was prevented by inhibitors of JAK/STAT, MAPK, and EGF receptors without inhibition of RSV replication. In lung tissue of an infant with severe RSV infection in which a few RSV antibody-positive macrophages were observed, MMP-10 was expressed at the apical side of the bronchial epithelial cells and alveolar epithelial cells. In conclusion, MMP-10 induced by RSV infection in HNECs is regulated via distinct signal transduction pathways with or without relation to RSV replication. MMP-10 may play an important role in the pathogenesis of RSV diseases and it has the potential to be a novel marker and therapeutic target for RSV infection.
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Obata
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nomura
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Obonai
authors.forename: Jun
authors.initials: J
authors.lastname: Fuchimoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D002648:Child; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053612:Janus Kinases / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism* / Q000821:virology*; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D053612:Janus Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; D053506:Matrix Metalloproteinase 10
keywords: MMP-10; RSV; human nasal epithelial cells; signal transduction; tight junctions