Ishinaga Hajime, Takeuchi Kazuhiko, Kishioka Chikako, Suzuki Shinya, Basbaum Carol, Majima Yuichi
Department of Otorhinolaryngology, Mie University School of Medicine, Tsu, Mie, Japan.
Pharmacology. 2005 Feb;73(2):89-96. doi: 10.1159/000081294. Epub 2004 Oct 5.
Pranlukast is a selective cysteinyl leukotriene(1 )(cysLT(1)) receptor antagonist, and is now widely used in the treatment of asthma. The anti-asthmatic effect of pranlukast may be rendered not only by antileukotriene activity, but also by other pharmacological activity. This study was designed to investigate whether pranlukast had inhibitory effects on nuclear factor-kappaB (NF-kappaB) activation and mucin gene expression in cultured human epithelial cells. Luciferase assay was mainly used for analysis. Cultured epithelial cells were transfected with NF-kappaB luciferase vector, MUC2 or MUC5AC luciferase vectors. Lipopolysaccharide (LPS) significantly increased NF-kappaB activation in NCI-H292 cells, which was inhibited by the pretreatment by pranlukast in a dose-dependent manner. Either LTD(4) or pranlukast alone did not increase NF-kappaB activation in NCI-H292 cells. Pranlukast also inhibited NF-kappaB activation induced by phorbol 12-myristate 13-acetate (PMA). Pranlukast also significantly inhibited LPS-induced MUC2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis in NCI-H292 cells. Pranlukast also inhibited LPS-induced MUC2 gene expression in HM3-MUC2 cells. However, pranlukast did not inhibit MUC5AC gene transcription activity induced by lipoteichoic acid (LTA) in NCI-H292 cells. These results suggest that pranlukast may inhibit NF-kappaB activation and MUC2 gene transcription through pathways distinct from cysLT(1) receptor antagonism in cultured human epithelial cells.
普仑司特是一种选择性半胱氨酰白三烯1（cysLT1）受体拮抗剂，目前广泛应用于哮喘治疗。普仑司特的抗哮喘作用可能不仅通过抗白三烯活性，还通过其他药理活性来实现。本研究旨在调查普仑司特对培养的人上皮细胞中核因子-κB（NF-κB）激活和黏蛋白基因表达是否具有抑制作用。主要采用荧光素酶测定法进行分析。将培养的上皮细胞用NF-κB荧光素酶载体、MUC2或MUC5AC荧光素酶载体进行转染。脂多糖（LPS）显著增加了NCI-H292细胞中NF-κB的激活，而普仑司特预处理可呈剂量依赖性抑制这种激活。单独的白三烯D4（LTD4）或普仑司特均未增加NCI-H292细胞中NF-κB的激活。普仑司特还抑制了佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的NF-κB激活。通过逆转录-聚合酶链反应（RT-PCR）分析，普仑司特还显著抑制了NCI-H292细胞中LPS诱导的MUC2 mRNA表达。普仑司特也抑制了HM3-MUC2细胞中LPS诱导的MUC2基因表达。然而，普仑司特并未抑制NCI-H292细胞中脂磷壁酸（LTA）诱导的MUC5AC基因转录活性。这些结果表明，在培养的人上皮细胞中，普仑司特可能通过不同于cysLT1受体拮抗作用的途径抑制NF-κB激活和MUC2基因转录。
