Mometasone Furoate Suppresses PMA-Induced MUC-5AC and MUC-2 Production in Human Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor α (TNF-α) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. METHODS: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)–induction of mucin and TNF-α in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1–500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone (1 µg/mL) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-α in culture supernatants were measured using enzyme-linked immunosorbent assay. RESULTS: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-α. CONCLUSION: Our findings demonstrated that MF and BUD attenuated mucin and TNF-α production in PMA-induced human airway epithelial cells.

Effects of Lobetyolin, Lobetyol and Methyl linoleate on Secretion, Production and Gene Expression of MUC5AC Mucin from Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: In this study, we investigated whether lobetyolin, lobetyol, and methyl linoleate derived from Codonopsis pilosula affect MUC5AC mucin secretion, production, and gene expression from airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with lobetyolin, lobetyol, or methyl linoleate for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin gene expression, and mucin protein production and secretion were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Lobetyolin, lobetyol, and methyl linoleate inhibited the gene expression of MUC5AC mucin induced by PMA; lobetyolin did not affect PMA-induced MUC5AC mucin production. However, lobetyol and methyl linoleate inhibited the production of MUC5AC mucin; lobetyolin and lobetyol did not significantly affect PMA-induced MUC5AC mucin secretion from NCI-H292 cells. However, methyl linoleate decreased the MUC5AC mucin secretion. CONCLUSION: These results suggest that among the three compounds, methyl linoleate can regulate gene expression, production, and secretion of MUC5AC mucin by directly acting on the airway epithelial cells.

Effect of Prunetin on TNF-alpha-Induced MUC5AC Mucin Gene Expression, Production, Degradation of IkappaB and Translocation of NF-kappaB p65 in Human Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: We investigated whether prunetin significantly affects tumor necrosis factor-alpha (TNF-alpha)-induced MUC5AC mucin gene expression, production, inhibitory kappa B (IkappaB) degradation and nuclear factor kappa B (NF-kappaB) p65 translocation in human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with prunetin for 30 minutes and then stimulated with TNF-alpha for 24 hours or the indicated periods. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of prunetin on TNF-alpha-induced degradation of IkappaB and translocation of NF-kappaB p65 was investigated by western blot analysis. RESULTS: We found that incubation of NCI-H292 cells with prunetin significantly inhibited mucin production and down-regulated the MUC5AC gene expression induced by TNF-alpha. Prunetin inhibited TNF-alpha-induced degradation of IkappaB and translocation of NF-kappaB p65. CONCLUSION: This result suggests that prunetin inhibits the NF-kappaB signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production regulated by the NF-kappaB signaling pathway.

Regulation of Tumor Necrosis Factor-alpha-induced Airway Mucin Production and Gene Expression by Carbenoxolone, Prunetin, and Silibinin / 결핵및호흡기질환

BACKGROUND: In this study, we tried to investigate whether carbenoxolone, prunetin, and silibinin affect tumor necrosis factor (TNF)-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with each agent (carbenoxolone, prunetin, and silibinin) for 30 min and then stimulated with TNF-alpha for 24 hours. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. RESULTS: Carbenoxolone, prunetin and silibinin inhibited the production of MUC5AC mucin protein induced by TNF-alpha; the 3 compounds also inhibited the expression of MUC5AC mucin gene induced by TNF-alpha. CONCLUSION: This result suggests that carbenoxolone, prunetin and silibinin can inhibit mucin gene expression and production of mucin protein induced by TNF-alpha, by directly acting on airway epithelial cells.