Background/Aims: Leukotriene (LT) D4 has been shown to induce mucus secretion in the airways. Excessive mucus secretion characterizes airway inflammatory disease such as asthma, allergic rhinitis. However, little is known about the effect of LTD4 on mucin gene expression. The aim of this study was to investigate the effect of LTD4 on MUC2 gene expression in cultured epithelial cells (HM3-MUC2 cells). Methods: HM3-MUC2 cells were treated with LTD4 for 2 or 6 h. Reporter gene assay was mainly used for analysis.MUC2 protein levels were measured using an enzyme-linked immunosorbent assay. Results: LTD4 significantly increased MUC2 gene transcriptional activity in a dose-dependent manner. Pranlukast, which is a selective antagonist of CysLT1 receptor, inhibited LTD4-induced MUC2 gene transcriptional activity in a dose-dependent manner. LTD4-induced MUC2 gene transcriptional activity was also suppressed by a G-protein inhibitor (pertussis toxin),a protein kinase C (PKC) inhibitor (bisindolylmaleimide), a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), an extracellular signal regulated kinase-2 (ERK-2) inhibitor (AG126) and a nuclear factor ĸB (NF-ĸB) inhibitor. In addition, pranlukast inhibited LTD4-induced NF-ĸB activity. Conclusion: These results suggest that LTD4 upregulates MUC2 gene transcription via a signaling pathway involving CysLT1 receptor, G-protein, PKC, MEK, ERK and NF-ĸB.

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