Extracellular signal-regulated kinase is involved in tumor necrosis factor-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells

Abstract

Objectives—Mucus secretion and inflammatory cytokines are increased in cases of chronic sinusitis with polyp. In this study we initially investigated the localization of MUC5AC protein in human nasal polyps. We then examined whether tumor necrosis factor-α (TNF-α) induces MUC5AC gene expression and whether extracellular signal-regulated kinase (ERK) plays a role in TNF-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. Finally, we investigated whether MUC5AC and activated ERK are co-expressed in goblet cells.Material and Methods—Human nasal polyp epithelial cells were isolated and subcultured. Passage-2 polyp epithelial cells were treated with 10 ng/ml TNF-α. ERK involvement was determined by Western blotting and MUC5AC gene expression by reverse transcriptase polymerase chain reaction. An ERK kinase assay and an inhibitor study using PD98059 were also performed. Immunohistochemical staining using polyclonal MUC5AC antibody and a phospho-specific ERK antibody was done in nasal polyps.Results—MUC5AC was found to be expressed in the majority of goblet cells in human nasal polyp epithelium. TNF-α induced MUC5AC gene expression, and ERK activation was found to be essential for TNF-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. In addition, both MUC5AC and activated ERK were co-expressed in goblet cells of human nasal polyp epithelium.Conclusions—TNF-α induces MUC5AC gene expression via ERK in cultured human nasal polyp epithelial cells.