The Effect of Omnaris(R) on the Inflammatory Reaction and Mucin Gene Expression from Nasal Polyp Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Glucocorticoids are a potent anti-inflammatory agent. The au-thors conducted this study to investigate the effect of Omnaris(R) on suppression of inflammation induction and mucin gene expression in nasal polyp epithelial cells. SUBJECTS AND METHOD: Primary nasal polyp epithelial cells were stimulated by 5 ug/mL of streptococcal enterotoxin B (SEB) and lipopolysaccharide (LPS). To determine the effects of Omnaris(R), cells were pretreated with 200, 100, 10, 1 ng/mL of Omnaris(R). The anti-inflammatory effect of epithelial cells were confirmed by measuring interleukin (IL)-6, IL-8, and granulocyte-macrophage colony stimulating factor (GM-CSF), and mucin gene expressions were determined by real time PCR for MUC4, MUC5AC, MUC5B, MUC8. RESULTS: SEB and LPS enhanced the production of IL-6, IL-8, and GM-CSF from nasal polyp epithelial cells. The increased cytokine levels were significantly suppressed by Omnaris(R) at 100 and 10 ng/mL. The expressions of MUC4, MUC5AC, MUC5B, MUC8 mRNA, and MUC4 mRNA were increased by SEB and LPS, respectively. The increased expression of these mucin genes were significantly suppressed by 100, 10, and 1 ng/mL of Omnaris(R). CONCLUSION: Omnaris(R) significantly suppressed the production of chemical mediators and mucin gene expression, which indicated that Omnaris(R) is effective in improving and treating inflammatory diseases in the nasal cavity.

Effects of Fungi and Eosinophils on Mucin Gene Expression in Rhinovirus-Infected Nasal Epithelial Cells

PURPOSE: Fungi, rhinoviruses (RVs), and eosinophils are associated with upper respiratory diseases. We evaluated the effects of fungal stimulation and eosinophil co-culture on the expression of mucin genes in RV-infected nasal polyp epithelial cells. METHODS: Nasal polyp epithelial cells were obtained from chronic rhinosinusitis patients. Cultured epithelial cells were stimulated with Alternaria and Aspergillus with or without RV-16 infection. The epithelial cells were co-cultured with eosinophils for 16 h. MUC4, MUC5AC, MUC5B, and MUC8 mRNA expressions in the epithelial cells were quantified using real-time RT-PCR. To determine the underlying mechanism, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and mitogen-activated protein kinase (MAPK) inhibitors were used to inhibit mucin gene expression. RESULTS: Fungi and RV-16 induced mucin gene expression in nasal polyp epithelial cells. However, there was no synergistic increase in mucin gene expression, with the exception of MUC4 mRNA expression stimulated by 25 microg/mL Aspergillus. When RV-16-infected epithelial cells were stimulated with fungi and then co-cultured with eosinophils, MUC4, MUC5B, and MUC8 mRNA expressions increased. Mucin gene expression was inhibited by NF-kappaB inhibitors. CONCLUSIONS: RV-16, airborne fungi, and eosinophils may exacerbate the inflammatory process in nasal mucosal diseases by enhancing mucin gene expression.

Interactions of Human T Cell Immunoglobin Mucins with Apoptotic Cells / 华中科技大学学报（医学）（英德文版）

T cell immunoglobulin mucin (TIM) family playsa key role in regulating immune responses.In this study,the interactions of human TIM family with apoptotic cells were evaluated in order to provide a foundation for further study on the roles of human TIM genes in apoptosis.Nine kinds of pEGFP-N1 eukaryotic expression vectors containing different lengths of the three members of human TIM genes for the expression of TIM-EGFP and the vectors for the expression of TIM-Fc fusion proteins were constructed.It was found that human TIM proteins could recognize and bind to apoptotic cells directly,but not to viable cells.The interactions of sTIM-1-EGFP,sTIM-3-EGFP and sTIM-4-EGFP with apoptotic cells were blocked by TIM-1-Ig,TIM-3-Ig and TIM-4-Ig fusion proteins respectively.In addition,human TIM proteins mediated the recognition of apoptotic cells and bound to apoptotic cells directly via the IgV domains.In conclusion,the TIM family may play a key role in the regulation of apoptosis.Our data also suggest that human TIM proteins probably serve as novel proteins for the detection of the early cellular apoptosis.

Prophylactic Effect of Lactobacillus GG in Animal Colitis and Its Effect on Cytokine Secretion and Mucin Gene Expressions / 대한소화기학회지

BACKGROUND/AIMS: Lactobacillus rhamnosus GG (LGG) has been used in acute colitis treatment. However, it is unclear whether the LGG prevents chronic colitis. The aim of this study was to examine the prophylactic effect of LGG on animal colitis, cytokine secretion, and mucin gene expression. METHODS: BALB/c mice (n=64) were exposed to 5% dextran sulfate sodium (DSS) for 7 days followed by 10 days recovery period and repeatedly exposed for 4 days. Then, the mice were devided into three group; group of oral LGG adminstration throughout the recovery and repeated colitis period; PBS group of PBS administration; control group. Colon length, histologic score, tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) levels, mucin gene expressions were determined at each period. RESULTS: In acute colitis period, the LGG group showed higher levels of disease activity index (DAI), histologic score, TNF-alpha, IL-10, but shorter colon length, lower levels of mucin gene expressions than the control group. However, in repeated colitis period, the LGG group showed markedly lower levels of DAI and IL-10 but significantly longer colon length than PBS group (p<0.05). There was no difference in the mucin gene expression. CONCLUSIONS: These results suggest that LGG prevents chronic murine colitis. It may be associated with cytokine modulation and competitive inhibition of pathogenic bacteria. However, it may not be related with gene expression.

Expression and regulation of MUC8 & MUC5AC by various cytokines in normal human nasal epithelial cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Sinusitis is one of the most commonly reported diseases in the world. A network of inflammatory mediators is known to be involved in the pathogenesis of chronic sinusitis and nasal mucus secretion may also be under the control of an inflammatory mediator network. To date, 12 human mucin genes have been identified; however, the regulation of MUC8 has not yet been found out. In this study, we described the regulation of the MUC8 mRNA expression by inflammatory mediators and investigated its cellular location. MATERIALS AND METHOD: MUC8 mRNA and MUC5AC mRNA were detected in culture using passage-2 normal human nasal epithelial (NHNE) cells after the treatment with a mixture of following inflammatory mediators; TNF-alpha, IL-1beta, LPS, IL-4, PAF. The translocation of MUC8 mRNA from the nucleus to the cytoplasm was investigated by treating the inflammatory mediators with in situ hybridization. RESULTS: We found that a mixture of inflammatory mediators increased the MUC8 mRNA expression but decreased the MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among the inflammatory mediators, Interleukin-4 was responsible for the decrease in the MUC5AC mRNA expression and the MUC5AC mucin secretion. We also found that MUC8 mRNA resides in the nucleus of goblet cells and is transported into the cytoplasm following the treatment with inflammatory mediators. CONCLUSION: These results indicate that MUC8 may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis.

Mucin and Lysozyme Expression in the Epithelium of Normal Human Nasal Inferior Turbinate and Polyps / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In chronic bronchitis, rhinitis or cystic fibrosis, the number of goblet cells increases along with hypertrophy of mucous cells in submucosal gland, resulting ineffective mucociliary clearance. But, it is still not fully understood what role each gene plays in producing airway secretions. This study aimed to figure out which mucin gene is expressed in the epithelium of normal human nasal mucosa and nasal polyps, and to verify whether the epithelium of nasal polyp itself contributes to the increased nasal secretion as in chronic sinusitis with nasal polyp. MATERIALS AND METHODS: Normal nasal epithelial cells were obt assay. And, RT-PCR was used for the detection of mucin mRNA and lysozyme mRNA. RESULTS: The level of intracellular mucin was 2.9 times higher in the epithelium of nasal polyp, and this was statistically significant. Among seven mucin genes (MUC1, 2, 4, 5AC, 5B, 7, 8) expressed in the epithelium of normal inferior turbinate and polyps, MUC2 and MUC8 were more strongly expressed in the epithelium of nasal polyp than those of normal inferior turbinate. CONCLUSION: This results suggest that the polyp epithelium itself is contributing to increased secretion in chronic sinusitis, and MUC2 and MUC8 are thought tbe responsible for this change. However, further study is required to uncover the full sequence of MUC8 mRNA and its exact function.