Effect of Resolvin D1 and E1 on Mucin Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin is an important component of mucus that performs the first line of defense against inhaled pathogens and particles, lubrication of organs, and protection of airway. It is hyper-secreted in inflammatory airway diseases and is associated with morbidity and mortality of the affected patients. Resolvin, an autacoid of a specific lipid structure, exhibits anti-inflammatory property against inflammatory airway diseases although its effects on mucin secretion by human airway epithelial cells have not yet been demonstrated. In this regard, we investigated the effects of Resolvin on lipopolysaccharide (LPS)-induced mucin expression in human airway epithelial cells. MATERIALS AND METHOD: In mucin-producing human NCI-H292 epithelial cells, the effects and brief signaling pathways of Resolvin D1 (RvD1) and Resolvin E1 (RvE1) on the LPS-induced MUC4, MUC5AC, and MUC5B expression were investigated using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: RvD1 attenuated LPS-induced MUC4, MUC5AC, and MUC5B mRNA expression and protein production in human NCI-H292 cells while RvE1 did not. RvD1 significantly blocked LPS-induced activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while RvE1 did not. CONCLUSION: These results suggest that RvD1 attenuates LPS-induced MUC4, MUC5AC, and MUC5B expressions via ERK1/2 MAPK, p38 MAPK, and NF-κB signaling pathways in airway epithelial cells. Therefore, RvD1 may modulate the control of mucus-hypersecretion in inflammatory airway diseases.

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.

Effect of High-Insulin on MUC4, MUC5AC, and MUC5B Expression in Airway Epithelial Cells

BACKGROUND AND OBJECTIVES: Insulin is a peptide hormone that regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles. Insulin has been reported to be closely related to cardiovascular, respiratory, and endocrine disease. However, the effect of insulin on production of major mucins in human airway epithelial cells has not been reported. Therefore, this study investigated the relationship between high levels of insulin and mucin in human airway epithelial cells. MATERIALS AND METHODS: This study analyzed the effect of high level of insulin on MUC4, MUC5AC, and MUC5B expression using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay in human airway epithelial cells. RESULTS: In human NCI-H292 airway epithelial cells, high level of insulin significant increased MUC4, MUC5AC, and MUC5B mRNA expression and glycoprotein production. In the primary cultures of normal nasal epithelial cells, high level of insulin also increased MUC4, MUC5AC, and MUC5B expression. CONCLUSION: These results suggest that insulin plays a role in control of mucus hypersecretion in human airway epithelial cells.

Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma

BACKGROUND: Recent reports have indicated that overexpression of mucin (MUC) 1 and/or MUC4 correlates with the occurrence and progression of extra-hepatobiliary malignancy. In this study, we investigated the expression of MUC1 and MUC4 and their prognostic significance in gallbladder adenocarcinoma. METHODS: We examined 54 surgical gallbladder adenocarcinoma samples by immunohistochemistry for MUC1 and MUC4 expression. Staining was evaluated as a sum score of extent and intensity, dividing the samples into low and high expression groups. RESULTS: The low expression group for both MUC1 and MUC4 was 10 samples (18.5%), and the high expression group was 44 samples (81.5%). High MUC1 expression was significantly correlated with more differentiated tumors (p=0.033), whereas high expression of MUC4 correlated with negative nodal status (p=0.012). Other pathological features were not correlated with MUC expression. Multivariate cox regression analysis showed that neither MUC1 nor MUC4 expression correlated with survival. CONCLUSIONS: Although there were some correlations found, a prognostic role for either MUC1 or MUC4 expression in gallbladder carcinoma was not identified in this study. Further investigation is required.

Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma

BACKGROUND: Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance. METHODS: We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray. RESULTS: We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128). CONCLUSIONS: MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.

Expression and clinical significance of MUC1,MUC2,MUC4 and MUC5AC in pancreatic ductal adenocarcinoma / 中华胰腺病杂志

Objective To investigate the expression and clinical significance of MUC1,MUC2,MUC4 and MUC5AC in pancreatic ductal adenocarcinoma(PDA).Methods To analyze the expression profiles of MUC1,MUC2,MUC4 and MUC5AC in PDA(n=26),chronic pancreatitis(CP,n=4),normal pancreas(n=16)and intraductal papillary-mucinous neoplasm(IPMN)(n=2),solid-pseudo-papillary tumor of pancreas(SPT)(n=4),serous cystic neoplasm(SCN)(n=1)using immunohistochemistry.Results Positive staining with MUC1 Was exclusively found in normal pancreas and CP tissues(100%);the expression of MUC1,MUC4 and MUCSAC in PDA was 100%,88.5%(23/26)and 76.9%(20/26)in PDA tissue;MUC2 and MUC5AC were expressed in 2 samples of IPMN;none of the four mucins were expressed in Sfrr and SCN.There was no association between the expression of MUC4,MUC5AC and the clinicopathologic parameters in PDA(P＞0.05).Conclusions Multiple mucins were expressed in PDA.Measurement of the mucin profile including all 4 mueins(MUC1,MUC2,MUC4,and MUC5AC)may be helpful in the diagnosis and differential diagnosis of PDA.

Effect of Macrolide on the MUC4 Gene Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin secretion are highly increased by inflammatory airway diseases such as asthma, chronic bronchitis and rhinosinusitis. Macrolide antibiotics is considered one of the effective drugs inhibiting mucus secretion for chronic bronchitis and rhinosinusitis with nasal polyp. However, the anti-secretory effect of macrolide is not clear. This study was designed to investigate whether macrolide can suppress interleukin-1beta (IL-1beta)-induced MUC4 gene expression and mucin secretion in the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. SUBJECTS AND METHOD: Nasal polyps were obtained from 20 patients with chronic rhinosinusitis with nasal polyp during endoscopic sinus surgery. We observed the effect of roxithromycin on the IL-1beta-induced MUC4 gene and mucin secretion by reverse transcriptase-polymerase chain reaction (RT-PCR) with enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Roxithromycin attenuated the IL-1beta-induced MUC4 mRNA expression and mucin secretion with a dose dependent pattern in both of the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. CONCLUSION: This result suggests that roxithromycin may be considered as an effective anti-hypersecretory agent for its down-regulation of the MUC4 gene.

Effects of Dexamethasone on Mucins of Human Corneal Epithelial Cells

PURPOSE: To evaluate whether mucin gene expression is regulated by glucocorticoid hormone in cultured human corneal epithelial cells (HCECs). The effects of dexamethasone on the expression of MUC1 and MUC4, two known mucins produced by corneal epithelial cells, were determined. METHODS: HCECs were cultured in medium supplemented with dexamethasone. The modulations of MUC1 and MUC4 expression by dexamethasone were investigated by RT-PCR and Western blot analysis. RESULTS: The expression of MUC1 mRNA and its protein were enhanced in HCECs by dexamethasone. However, the treatment of HCECs with dexamethasone caused a decrease in MUC4 mRNA and its protein. These effects of dexamethasone on the MUC1 and MUC4 were abolished by a glucocorticoid antagonist (RU486). CONCLUSIONS: This study shows that dexamethasone is implicated in the expression of mucin in HCECs, and suggests that glucocorticoid receptor participates in the modulation of mucin production.