Montelukast Inhibits Leukotriene Stimulation of Human Dendritic Cells in vitroIlarraza R.a · Wu Y.a · Adamko D.J.a, b
Pulmonary Research Group, Departments of aPediatrics and bMedicine, University of Alberta, Edmonton, Alta., Canada
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Background: Leukotrienes are potent inflammatory mediators which modulate immune responses and induce bronchoconstriction in susceptible individuals. Montelukast (MK) is a leukotriene receptor (CysLT1) antagonist that has been shown to prevent exacerbation of asthma. Considering the plethora of potential cellular targets for MK, specific mechanisms for its therapeutic action are still not fully understood. In vitro, we determined whether human dendritic cell function could be affected by leukotriene C4 (LTC4) treatment and whether MK had potential in modulating this response. We also studied the effect of LTC4 in the context of response to an airway virus (respiratory syncytial virus, RSV). Methods: Human monocyte-derived dendritic cells (moDCs) exposed to LTC4, MK, or both, were cocultured with autologous T cells, with or without RSV. The effects of LTC4 and MK on cell function were determined by ELISA and proliferation assays. Results: Both moDCs and their precursors – monocytes – express LTC4 receptor CysLT1, making them potential targets for MK. moDCs cultured with LTC4 release the eosinophil chemoattractant RANTES (CCL5) and induce greater T cell proliferation. Both were blocked by the presence of MK. MK treatment, albeit anti-inflammatory, did not interfere with the moDC-dependent T cell-proliferative responses induced by RSV. Conclusions: LTC4, chronically present in the airways of asthma patients, could induce an exaggerated inflammatory response to airway infection via dendritic cell activation, which would be prevented by MK. Our study provides additional insight into the mechanisms of action of this leukotriene receptor antagonist.
© 2012 S. Karger AG, Basel
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