title: Tiotropium bromide attenuates respiratory syncytial virus replication in epithelial cells.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) infection could be related to airway inflammation as well as exacerbation of chronic obstructive pulmonary disease (COPD). Tiotropium bromide decreases the frequency of exacerbation in patients with COPD; however, the mechanisms of tiotropium bromide to reduce the chances of exacerbation have not been defined. One potential mechanism could be that tiotropium bromide protects against RSV infection in epithelial cells.
  
  
  OBJECTIVE
  To examine whether tiotropium bromide affects RSV replication in HEp-2 cells.
  
  
  METHODS
  The supernatant titer of RSV was calculated by methylcellulose plaque assay after RSV innoculation. Intracellular RSV and ICAM-1 mRNA were measured by PCR. Syncytium formation was observed by light microscopy. Intracellular RSV fusion protein and RhoA protein were detected by Western blot analysis. Furthermore, RhoA activity, ICAM-1 expression and inflammatory cytokines in cultured supernatant were measured by binding assay, immunofluorescence staining and ELISA, respectively.
  
  
  RESULTS
  Tiotropium bromide decreased the supernatant titer of RSV, and it inhibited syncytium formation, RhoA activation and ICAM-1 expression. Moreover, it suppressed the production of IL-6 and IL-8 after RSV infection.
  
  
  CONCLUSIONS
  The antiviral effects of tiotropium bromide regarding RSV replication are partly due to inhibition of RhoA activity and ICAM-1 expression. Tiotropium bromide decreases RSV replication and may modulate airway inflammation by reducing the production of inflammatory cytokines.
authors: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Ken
authors: K
authors: Iesato
authors: Koichiro
authors: K
authors: Tatsumi
authors: Kengo
authors: K
authors: Saito
authors: Takashi
authors: T
authors: Ogasawara
authors: Seiichiro
authors: S
authors: Sakao
authors: Yuji
authors: Y
authors: Tada
authors: Yasunori
authors: Y
authors: Kasahara
authors: Katsushi
authors: K
authors: Kurosu
authors: Nobuhiro
authors: N
authors: Tanabe
authors: Yuichi
authors: Y
authors: Takiguchi
authors: Takayuki
authors: T
authors: Kuriyama
authors: Hiroshi
authors: H
authors: Shirasawa
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015726:Giant Cells / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D000069447:Tiotropium Bromide; D014760:Viral Fusion Proteins / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors
chemical_list: D000998:Antiviral Agents; D018680:Cholinergic Antagonists; D015850:Interleukin-6; D016209:Interleukin-8; D012367:RNA, Viral; D012602:Scopolamine Derivatives; D014760:Viral Fusion Proteins; D018799:Intercellular Adhesion Molecule-1; D020742:rhoA GTP-Binding Protein; D000069447:Tiotropium Bromide