Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.
BACKGROUND: Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation. METHODS: Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues. RESULTS: Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production. CONCLUSION: Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.
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Pranlukast Pranlukast cysteinyl leukotrienes pranlukast pranlukast cysteinyl leukotriene pranlukast dexamethasone pranlukast pranlukast dexamethasone Pranlukast leukotriene leukotriene CysLTR1 IL-5 CysLTR1 IL-5 IL-5 CysLTR1 interleukin-5 IL-5 cysteinyl leukotriene receptor 1 IL-5 CysLTR1 IL-5 CysLTR1 IL-5 IL-5 leukotriene receptor leukotriene receptor interleukin-5