Modulation of IL-8 mRNA expression and production in respiratory syncytial virus (RSV) stimulated human alveolar epithelial cells by budesonide and montelukast

Abstract

Rationale Pediatric bronchiolitis and the subsequent development of asthma can be triggered by RSV infection. Alveolar epithelial cell stimulation by RSV leads to cytokine release and can damage the airway epithelium. IL-8 is a potent neutrophil chemoattractant expressed in RSV stimulated human bronchial epithelium. Budesonide and montelukast both have a potential role in regulating IL-8 in human alveolar epithelial cells. Methods Human alveolar epithelial (A549) cells (1×10 6 cells/ml) were assessed for IL-8 production and expression at 17 and 48 hours using a quantitative colorimetric ELISA and a gene-specific quantitative mRNA assay. Cells were incubated in the presence of 265 μg/ml of RSV antigen and/or 100 U/ml of IL-1β and treated with 50 μM of montelukast or 1×10 −7 M of budesonide. Results A549 cells stimulated with RSV, IL-1β, and RSV+IL-1β showed a significant increase in the production and expression of IL-8 at 17 (p<.05) and 48 hours (p<.05) over cells alone, except for RSV stimulation alone which did not increase IL-8 mRNA expression above control at 17 hours. IL-1β and RSV+IL-1β stimulated cells showed a significant decrease in the production and expression of IL-8 at 17 (p<.05) and 48 hours (p<.05) when incubated with budesonide, and a non-significant decrease when incubated with montelukast. Conclusion Treatment of A549 cells stimulated with RSV and IL-1β with montelukast and budesonide resulted in a decrease in production and expression of IL-8. This suggests that budesonide and montelukast may play a role in regulating IL-8, an important mediator of inflammation in the human airway and asthma.