인간 호흡기 상피세포에서 MUC5B 발현에 대한 Udenafil의 효과
Effect of Udenafil on MUC5B Expression in Human Airway Epithelial Cells
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Background and Objectives Mucus hypersecretion in the airway may lead to increased frequency and duration of infection, declined lung function, and increased morbidity and mortality in inflammatory respiratory diseases. Udenafil, a phosphodiesterase (PDE) 5 inhibitor, is an oral medication for erectile dysfunction. Recent studies show that PDE5 inhibitor has various anti-inflammatory properties. However, the effect of udenafil on mucus secretion in human airway epithelial cells is unclear. Therefore, the effect and brief signaling pathway of udenafil on MUC5B expression were investigated in human airway epithelial cells. Materials and Method We analyzed the effects and brief signaling pathway of udenafil on the lipopolysaccharide (LPS) induced MUC5B expression in mucin-producing NCI-H292 epithelial cells using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblot analysis. Results Udenafil attenuated the LPS-induced MUC5B mRNA expressions and glycoprotein production in NCI-H292 epithelial cells. It also attenuated LPS-induced toll like receptor 4 (TLR4) mRNA expression and phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and p38 in NCI-H292 epithelial cells. Conclusion These results suggest that udenafil attenuates the LPS induced MUC5B expression via TLR4, ERK1/2 and p38 mitogen activated protein kinase (MAPK) pathway in human airway epithelial cells, and that it could be a novel therapeutic agent for controlling chronic airway disease.
Abstract
Background and Objectives Mucus hypersecretion in the airway may lead to increased frequency and duration of infection, declined lung function, and increased morbidity and mortality in inflammatory respiratory diseases. Udenafil, a phosphodiesterase (PDE) 5 inhibitor, is an oral medication for erectile dysfunction. Recent studies show that PDE5 inhibitor has various anti-inflammatory properties. However, the effect of udenafil on mucus secretion in human airway epithelial cells is unclear. Therefore, the effect and brief signaling pathway of udenafil on MUC5B expression were investigated in human airway epithelial cells. Materials and Method We analyzed the effects and brief signaling pathway of udenafil on the lipopolysaccharide (LPS) induced MUC5B expression in mucin-producing NCI-H292 epithelial cells using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblot analysis. Results Udenafil attenuated the LPS-induced MUC5B mRNA expressions and glycoprotein production in NCI-H292 epithelial cells. It also attenuated LPS-induced toll like receptor 4 (TLR4) mRNA expression and phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and p38 in NCI-H292 epithelial cells. Conclusion These results suggest that udenafil attenuates the LPS induced MUC5B expression via TLR4, ERK1/2 and p38 mitogen activated protein kinase (MAPK) pathway in human airway epithelial cells, and that it could be a novel therapeutic agent for controlling chronic airway disease.
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