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

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 (LTC4S) messenger RNA (mRNA) expression in 16-HBEC was detected using fluorescence quantitative polymerase chain reaction, and the relative level of LTC4S 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 LTC4S expression and CysLT secretion. Results: RSV infection resulted in increased LTC4S 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 LTC4S mRNA expression. Conclusions: RSV infection upregulated LTC4S 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.