Modulation of endothelin-1 expression in pulmonary epithelial cell line (A549) after exposure to RSV

Respiratory syncytial virus (RSV) is one of the most important respiratory tract pathogens in infants and young children. The airway epithelial cells are the primary target cells for RSV infection. The airway epithelial layer is not only a physical barrier, but also plays a role in a synthesis of a variety of major inflammatory cytokines (IL-6, IL-8, GM-CSF etc.) as previo usly reported. Endothelin-1 (ET-1) is a potent bronchoconstrictor and vasoc onstrictor factor, and involved in pathogenesis of various diseases of the respiratory tract. We hypothesized that RSV may induce the release of ET-1 from the bronchial epithelial cell line. No previous data is available rega rding association between RSV infection and ET-1 release. We evaluated the effect of RSV with different concentrations of RSV (MOI 0.1, 1 and 3 pfu/ce ll) on bronchial epithelial cell line (A549) and measured the production of ET-1 at both protein and mRNA level. A549 cells were treated with differen t conditions by using LPS, heat-inactivated RSV, RSV or medium alone as con trol. We observed time-dependent ET-1 release by RSV-infected A549 cells at 4 h, 24 h and maximum at 72 h. ET-1 was expressed in unstimulated A549 cel ls and was further increased by RSV. RSV with concentration MOI 0.1 (pfu/ce ll) and LPS appeared to have strongest stimulation on production of ET-1. I n addition, ET-1 mRNA was increased significantly by 16 h and decreased to relatively low-level at 24 h. These experiments suggested that airway epith elial cells might play a role in the local airway smooth muscle tone throug h the production of endothelin-1 during RSV infection.