Respiration
Basic Science Investigations
Tiotropium Bromide Attenuates Respiratory Syncytial Virus Replication in Epithelial CellsIesato K.a, b · Tatsumi K.a · Saito K.b · Ogasawara T.a · Sakao S.a · Tada Y.a · Kasahara Y.a · Kurosu K.a · Tanabe N.a · Takiguchi Y.a · Kuriyama T.a · Shirasawa H.bDepartments of aRespirology and bMolecular Virology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Article / Publication Details
Received: January 10, 2008
Accepted: June 02, 2008
Published online: August 26, 2008
Issue release date: November 2008
Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 0
ISSN: 0025-7931 (Print)
eISSN: 1423-0356 (Online)
For additional information: https://www.karger.com/RES
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.
© 2008 S. Karger AG, Basel
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Article / Publication Details
Received: January 10, 2008
Accepted: June 02, 2008
Published online: August 26, 2008
Issue release date: November 2008
Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 0
ISSN: 0025-7931 (Print)
eISSN: 1423-0356 (Online)
For additional information: https://www.karger.com/RES
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