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Pranlukast, a Leukotriene Receptor Antagonist, Inhibits Interleukin-5 Production via a Mechanism Distinct from Leukotriene Receptor Antagonism

2005; Karger Publishers; Volume: 136; Issue: 2 Linguagem: Inglês

10.1159/000083325

1423-0097

Chizu Fukushima, Hiroto Matsuse, Yoshitaka Hishikawa, Yuki Kondo, Ikuko Machida, Sachiko Saeki, Tetsuya Kawano, Shinya Tomari, Yasushi Obase, Terufumi Shimoda, Takehiko Koji, Shigeru Kohno,

Respiratory and Cough-Related Research

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.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.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.Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.