Respiratory syncytial virus induces leukotriene C4 synthase expression in bronchial epithelial cells

Respirology. 2013 Nov:18 Suppl 3:40-6. doi: 10.1111/resp.12188.

Abstract

Background and objective: Respiratory syncytial virus (RSV) results in acute wheezing in infants and is frequently associated with recurrent wheezing. Although RSV-induced wheezing clinically resembles that of asthma, corticosteroids are not equivalently effective in RSV-associated wheezing. The study sought to determine the mechanisms of RSV-induced wheezing by establishing an in vitro model of RSV-infected human bronchial epithelial cells (16-HBEC).

Methods: Leukotriene C4 synthase (LTC4 S) messenger RNA (mRNA) expression in 16-HBEC was detected using fluorescence quantitative polymerase chain reaction, and the relative level of LTC4 S mRNA was expressed as quotient cycle threshold (qCt) based on the threshold cycle number value compared with that of β-actin. Cysteinyl leukotrienes (CysLT) in culture supernatant were measured by enzyme-linked immunosorbent assay. RSV-infected 16-HBEC was incubated with gradient concentration of budesonide (BUD) to assess its effects on LTC4 S expression and CysLT secretion.

Results: RSV infection resulted in increased LTC4 S mRNA expression between 48 and 96 h post-infection. High level of CysLT was detected in the supernatant of RSV-infected 16-HBEC. BUD at concentrations of 10(-10) to 10(-5) mol/L did not significantly alter LTC4 S mRNA expression.

Conclusions: RSV infection upregulated LTC4 S expression in HBEC leading to increased CysLT secretion. Such induction was not attenuated by BUD, suggesting that CysLT might contribute to the pathogenesis of RSV-induced wheezing.

Keywords: bronchial epithelial cell; corticosteroid; cysteinyl leukotriene; respiratory syncytial virus.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Asthma / metabolism*
  • Asthma / pathology
  • Asthma / virology*
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Bronchi / virology
  • Budesonide / pharmacology
  • Cell Line
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Glutathione Transferase / metabolism*
  • Humans
  • In Vitro Techniques
  • RNA, Messenger / metabolism
  • Receptors, Leukotriene / metabolism
  • Respiratory Syncytial Virus Infections / complications
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / physiology*
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • RNA, Messenger
  • Receptors, Leukotriene
  • Budesonide
  • Glutathione Transferase
  • leukotriene-C4 synthase
  • leukotriene D4 receptor