Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MUC5AC is one of the major secretory mucin genes in the human airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to have anti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucin secretion of airway epithelial cells still have not been reported. Therefore, the aim of this study is to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expression in human airway epithelial cells. MATERIALS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerase chain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC) as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPS-induced ROS production in human NCI-H292 cells. RESULTS: LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. In addition, NAC and apocynin inhibited LPS-induced MUC5AC mRNA expression and protein production. CONCLUSION: These results demonstrate that PPD inhibits LPS-induced MUC5AC expression via ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that of NAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control of mucus secretion and oxidative stress in human airway epithelial cells.

Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#MUC5AC is one of the major secretory mucin genes in the human airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to have anti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucin secretion of airway epithelial cells still have not been reported. Therefore, the aim of this study is to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expression in human airway epithelial cells. MATERIALS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerase chain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC) as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPS-induced ROS production in human NCI-H292 cells. @*RESULTS@#LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. In addition, NAC and apocynin inhibited LPS-induced MUC5AC mRNA expression and protein production. @*CONCLUSION@#These results demonstrate that PPD inhibits LPS-induced MUC5AC expression via ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that of NAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control of mucus secretion and oxidative stress in human airway epithelial cells.

High Concentration of Glucose Induces MUC5B Expression via Reactive Oxygen Species in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The effects of hyperglycemia on the mucin secretion in inflammatory respiratory diseases are not clear. Therefore, this study was conducted to characterize the effect of hyperglycemia, and the mechanism involved, on MUC5AC and MUC5B expression in human airway epithelial cells. SUBJECTS AND METHOD: The NCI-H292 cells and the primary cultures of human nasal epithelial cells were exposed to different concentration of glucose (5, 10, 15, 20, 30 mM) for 8 or 24 hours, the effects of high concentration of glucose (20 mM) on MUC5AC and MUC5B expression were determined using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR and enzyme immunoassay. Measurement of reactive oxygen species (ROS) production was performed by flow cytometry. To investigate the role of ROS in high concentration of glucose-induced MUC5B expression, the cells were pretreated with N-acetyl-cysteine (NAC, 50 mM) as a ROS scavenger, or diphenyleneiodonium (DPI, 100 nM) as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor for 1 hour. RESULTS: In the NCI-H292 cells and the primary cultures of human nasal epithelial cells, High concentration of glucose increased MUC5B expression but did not increase MUC5AC expression (p<0.05). ROS production was also increased by high concentration of glucose (20 mM) (p<0.05). In addition, high concentration of glucose (20 mM)-induced MUC5B expression and ROS production were significantly attenuated by pretreatment of NAC (50 mM) or DPI (100 nM) (p<0.05). CONCLUSION: High concentration of glucose induces MUC5B expressions via ROS in human airway epithelial cells.

Asian Sand Dust Up-Regulates MUC4 Expression in Human Upper Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Asian sand dust (ASD) is a meteorological phenomenon that occurs in spring time in Korea. ASD is composed of various organic and inorganic materials, which induce airway inflammation. MUC4 is an important membrane-bound mucin gene in the human airway, and its expression is increased in pathologic proliferative lesions such as nasal polyps. However, the effect of ASD on MUC4 in human airway epithelial cells is unclear. Therefore, this study aimed to investigate the effect and signaling pathway of ASD on MUC4 expressions in human airway epithelial cells. METERIALS AND METHOD: The effect and signaling pathway of ASD on MUC4 expressions were investigated in NCI-H292 cells and in the primary cultures of human nasal epithelial cells using reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering ribonucleic acid (siRNA). RESULTS: ASD induced MUC4 expression and the activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). An ERK1/2 MAPK inhibitor and a p38 MAPK inhibitor inhibited the ASD-induced MUC4 expression. In addition, the knockdowns of ERK1, ERK2 and p38 MAPK by the respective siRNA blocked the ASD-induced MUC4 mRNA expression. ASD induced toll-like receptor 4 (TLR4) mRNA expression. The knockdown of TLR4 by TLR4 siRNA blocked the phosphorylation of ERK1/2 and p38 MAPK, and the ASD-induced MUC4 mRNA expression. CONCLUSION: These results show that ASD induces MUC4 expressions via TLR4-dependent ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.