Leukotriene D4 upregulates MUC2 gene transcription in human epithelial cells.

Article Details

Citation

Copy to clipboard

Suzuki S, Takeuchi K, Ishinaga H, Basbaum C, Majima Y

Leukotriene D4 upregulates MUC2 gene transcription in human epithelial cells.

Pharmacology. 2008;81(3):221-8. doi: 10.1159/000112866. Epub 2008 Jan 7.

PubMed ID

18176092 [ View in PubMed

]

Abstract

BACKGROUND/AIMS: Leukotriene (LT) D(4) 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 LTD(4) on mucin gene expression. The aim of this study was to investigate the effect of LTD(4) on MUC2 gene expression in cultured epithelial cells (HM3-MUC2 cells). METHODS: HM3-MUC2 cells were treated with LTD(4) 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: LTD(4) significantly increased MUC2 gene transcriptional activity in a dose-dependent manner. Pranlukast, which is a selective antagonist of CysLT(1) receptor, inhibited LTD(4)-induced MUC2 gene transcriptional activity in a dose-dependent manner. LTD(4)-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 kappaB (NF-kappaB) inhibitor. In addition, pranlukast inhibited LTD(4)-induced NF-kappaB activity. CONCLUSION: These results suggest that LTD(4 )upregulates MUC2 gene transcription via a signaling pathway involving CysLT(1) receptor, G-protein, PKC, MEK, ERK and NF-kappaB.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pranlukast	Cysteinyl leukotriene receptor 1	Protein	Humans	Yes	Antagonist	Details