Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

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.

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

BACKGROUND: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). METHODS: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. RESULTS: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren's classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren's classification, pN stage, or pTNM stage. CONCLUSIONS: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma

Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.

Association of Helicobacter pylori with colorectal cancer development.

Background: Helicobacter pylori (H. pylori) may be associated with colorectal cancer. However, the underlying mechanisms are still unclear. Objectives: Explore the serostatus of H. pylori cytotoxicity-associated gene A product (CagA) in patients with colorectal carcinoma, and assess the association of H. pylori with colorectal cancer via c-Myc and MUC-2 proteins at tumor tissues. Methods: H. pylori CagA IgG antibodies were screened using enzyme-linked immunosorbent assay (ELISA) in 30 patients with colorectal carcinoma and 30 cancer-free control subjects. Paraffin-embedded blocks were examined for the expression of c-Myc and MUC-2 protein by immunohistochemistry. Results: H. pylori CagA seropositivity increased significantly among colorectal cancer patients (p <0.05). The expression of c-Myc and MUC-2 in colorectal carcinoma patients was over-expressed (80%), and downexpressed (63%) in resection margins (p <0.05). c-Myc over-expression and MUC-2 down-expression were associated with CagA-positive rather than CagA-negative H. pylori patients. In 16 CagA seropositive vs. 14 CagA seronegative patients, the expression rate was 97.3% vs. 64.2% and 33.3% vs. 78.5% for cMyc and MUC-2, respectively. CagA IgG level was significantly higher in positive than in negative c-Myc patients (p= 0.036), and in negative than in positive MUC-2 patients (p= 0.044). c-Myc and MUC-2 were positively and inversely correlated with CagA IgG level (p <0.05). Conclusions: CagA-seropositive H. pylori is most probably associated with colorectal cancer development. Part of the underlying mechanism for such association might be via alterations in expression of MUC-2, which depletes the mucous protective layer in the colo-rectum, and c-Myc, which stimulates the growth of cancerous cells.

Expression of protein MUC1 and MUC2 in intraductal papillary mucinous neoplasms and its significance / 第二军医大学学报

Objective: To investigate the expression of protein MUC1 and MUC2 in intraductal papillary mucinous neoplasms (IPMNs) and its significance. Methods: Immunohistochemical method (En Vision) was used to analyze the expression of protein MUC1 and MUC2 in 18 IPMNs and 9 pancreatic ductal adenocarcinomas. Results: Expression of protein MUC1 was detected in 4 of the 18 (22%) IPMNs (including 1 with pancreatic intraductal papillary-mucinous carcinoma) and all the 9 (100%) the pancreatic ductal adenocarcinomas, with the latter significantly higher than the former(P<0.01). Expression of protein MUC2 was detected in 17 of the 18 (94.4%) IPMNs and in 1 of the 9 (11.1%) pancreatic ductal adenocarcinomas, with the former significantly higher than the latter(P< 0.01). The expression levels of MUC2 were significantly different in IPMNs of different types (IPMA, IPMB, and IPMC, P<0.05). Conclusion: IPMNs have high expression of MUC2 and the expression is associated with the pathological types of IPMN. MUC1 expression may serve as a marker of malignant IPMNs and is worth further studying.

Methylation status of MUC2 gene in pancreatic carcinoma cell lines and peripheral blood of pancreatic carcinoma patients / 中华胰腺病杂志

Objective To analyze the methylation status of MUC2 gene in pancreatic carcinoma cell lines and peripheral blood of pancreatic carcinoma patients,and to explore the role of MUC2 methylation in the early diagnosis of pancreatic carcinoma.Methods Human pancreatic cancer cell lines of SW1990,ASPC,PANC1,BxPC3,PaTu8988 and CFPAC1,and 40 peripheral blood samples of pancreatic carcinoma patients,15 cases of chronic pancreatitis,25 cases of normal controls were collected,and the methylation status of MUC2 gene was detected by methylation sensitive restriction endonuclease PCR.Results MUC2 methylation was not detected in PANC1,BxPC3,PaTu8988,but was detected in ASPC,CFPAC1,SW1990.Among the peripheral blood samples,the rate of methylation in pancreatic cancer was 40.O%(n=16),in chronic pancreatitis was 0%,in normal controls was 4.0%(n=1),and the difference among the three groups was statistically significant(P＜0.01).The methylation of MUC2 gene CpG islands for the diagnosis of pancreatic carcinoma had a sensitivity of 40%,specificity of 97.5%,accuracy of 68.8%,positive predictive value of 94.1%and negative predictive value of 61.9%.Conclusions The detection of MUC2 hypermethylation in peripheral blood samples may be an potential marker for early diagnosis of pancreatic carcinoma.

Clinical Significance of MUC2 and MUC5AC Expression in Gastric Adenocarcinomas

PURPOSE: We examined the clinical significance of MUC2 and MUC5AC gene expression in gastric adeno-carcinoma tissues. METHODS: Two hundred specimens were obtained from gastric carcinoma patients who underwent gastric cancer operations at Samsung Medical Center between January 2001 and January 2005. MUC2 and MUC5AC expression were examined immunohistochemically, and correlated with clinicopathologic features and prognostic significance. RESULTS: MUC2 expression was positive in 88 tissues (44.0%) and MUC5AC expression was positive in 125 tissues (62.5%). MUC2 expression was associated with cancer advancement, lymph node metastasis, T classification, distant metastasis, and endolymphatic invasion. Loss of MUC5AC expression was significantly related to cancer advancement, lymph node metastasis, advanced T stage, and distant metastasis. MUC2 expression was usually negative in early gastric cancer (78%), but usually positive in advanced gastric cancer (66%). MUC5AC was usually positive in early gastric cancer (74%). The prognosis of the MUC2(-) group was significantly better than the MUC2(+) group (P<0.001). There was no relationship with MUC5AC expression and survival. Multivariate analysis showed that T classification, lymph node metastasis, distant metastasis, endolymphatic invasion, and MUC2 expression were independent prognostic factors, but MUC5AC expression was not. CONCLUSION: MUC2 and MUC5AC expression correlated with several clinicopathologic parameters (cancer advancement, lymph node metastasis, advanced T classification, distant metastasis). MUC2 expression was a significant independent prognostic factor and positive MUC2 expression suggested poor prognosis. MUC2 expression may have prognostic significance in gastric adeno-carcinomas.

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.

Associated Expression Mucin MUC1、MUC2 and Matrix Metalloproteinase (MMP-3) in Colorectal Carcinoma and Their Clinical Significance / 医学研究杂志

Objective To explore the relationship between the associated expression of mucin MUC1、MUC2、Matrix Metalloproteinase(MMP-3)and clinicopathological parameters in colorectal adenoma and colorectal carcinoma.Methods The expression of MUC1、MUC2 and MMP-3 were detected in 20 colorectal adenomas and 60 colorectal carcinomas by immunohistochemical method.Results The positive expression rates of MUC1 、MUC2 and MMP-3 in 20 colorectal adenomas and 60 colorectal carcinomas were 10% 、46.7%(P=0.013);100%、58.3%(P=0.000);10%、41.7%(P=0.031)respectively.The expression of mucin MUC1 was negative correlated to the degree of differentiation(P=0.006),but positively correlated to the depth of invasion(P=0.004),lymph node metastasis(P=0.010),Dukes staging(P=0.033)and negafively correlated with proghosis.Mucin MUC2 expression was unrelated to differentiation(P=0.143),but negative correlated to the depth of invasion(P=0.016),lymph node metastasis(P=0.002).Dukes staging(P=0.005)and posifively correlated with survival period.The positive expression of MMP-3 was positively correlated to lymph node metastasis(P=0.002),but negatively correlated to prognosis.Associated detection of MUC1 、MUC2 and MMP-3 showed that MUC1 was negatively correlated to MUC2,MUC2+MUC1-gave the best prognosis,while MUC1+MUC2-gave the worst prognosis.Conclusions The up-regulation of MUC1、MMP-3 expression or down-regulation of MUC2 expression may be involved in carcinogenesis,progression,invasion and metastasis.And it is very important to predict the prognosis in colorectal carcinomas.

Expression of MUC Gene Proteins in Cholecystitis, Adenoma and Adenocarcinoma of the Gallbladder

PURPOSE: Normal gallbladder mucosa shows unique and diverse patterns of mucin genes, and altered mucin expressions have been noted in the gallbladders with stones, dysplasia or carcinomas. The aim of this study was to characterize the expressions of MUC gene proteins in cholecystitis, adenoma and adenocarcinoma of the gallbladder. Differences of MUCs expressions according to the histopathologic parameters in gallbladder carcinomas were also studied. METHODS: Three tissue microarray blocks were made from 23 cases of cholecystitis, 40 cases of gallbladder adenoma, and 66 cases of gallbladder adenocarcinoma. Immunohistochemical stains for MUC1, MUC2, MUC4, MUC5AC and MUC6 were performed, and staining intensity and patterns were evaluated. RESULTS: MUC1, MUC2, MUC4, MUC5AC and MUC6 were overexpressed in 86 (66.7%), 20 (15.5%), 68 (52.7%), 74 (57.4%) and 47 (36.4%) of gallbladder lesions, respectively. MUC1 and MUC2 overexpression rates were higher in gallbladder carcinoma than in cholecystitis and gallbladder adenoma (P<0.05). MUC6 overexpression rate was higher in gallbladder adenoma than in cholecystitis and gallbladder carcinoma (P<0.05). Overexpression of MUC4 and MUC5AC showed no significant differences in cholecystitis, gallbladder adenoma and gallbladder carcinoma. In gallbladder carcinomas MUC1 overexpression rate was high in cases with deeper tumor invasion (P<0.05). MUC6 overexpression rate decreased in cases with larger tumor (P<0.05), higher histologic grade (P=NS), and deeper invasion (P=NS). MUC2, MUC4 and MUC5AC overexpression rates had no relations to the histopathologic parameters. CONCLUSION: Carcinomatous change of gallbladder may be related to MUC1 and MUC2 overexpressions. MUC1 overexpression seems to be related to aggressive biologic behavior of gallbladder carcinoma. MUC6 overexpression acts as a good prognostic factor.

Expression of MUC2 and MUC6 in Colorectal Adenomas and Adenocarcinomas

PURPOSE: Although the expression of MUC2 is seen in colorectal tumors, there have been few reports about the expression of MUC6 in colorectal tumors. The aim of this study was to investigate the expressions of MUC2 and MUC6 in normal colorectal tissues and in tumors, as well as the association of MUC2 and MUC6 expressions with prognostic factors. METHODS: Twenty (20) cases of colorectal adenomas treated by using a endoscopic polypectomy and 30 cases of colorectal carcinomas treated by using a resection were collected. Ten (10) normal tissue samples were obtained apart from the carcinomas. Sections were used for MUC2 and MUC6 immunostaining. The expressions of MUC2 and MUC6 were scored by using the sum of the percentages of the stained cells and the intensity of staining. RESULTS: All of the ten normal colorectal tissues expressed MUC2 and MUC6. Of the 20 adenomas, 19 cases (95%) were MUC2 positive, and 17 cases (85%) were MUC6 positive. Adenomas with severe atypia tended to express lower levels of MUC2 and MUC6 than those with mild or moderate atypia. Of the 30 carcinomas, 28 cases (93%) were MUC2 positive and 19 cases (63.3%) were MUC6 positive. Colorectal mucinous carcinomas differed significantly from non-mucinous carcinomas in strong MUC6 expression. MUC2 expression showed a significant association with lymph-node metastasis. CONCLUSIONS: The results suggest that MUC6 is expressed in normal colorectal tissues and tumors, that MUC6 expression is especially strong in mucinous carcinomas, and that MUC2 expression is associated with lymph-node metastasis, among the prognostic factors.

Expression Patterns of Tumor Related Proteins for Differential Diagnoses of Intrahepatic Adenocarcinomas

Background : Differential diagnoses of intrahepatic adenocarcinomas (IHAC) play an important role in the detecting primary sites and the determining type of treatment and overall prognosis of the patient. However, histopathologic findings alone have limitations of differential diagnoses of IHAC. Methods : To clarify which tumor related proteins (TRP) are useful for differential diagnoses of IHAC, TRP expression were investigated immunohistochemically, using MUC5AC, MUC2, mAb 91.9H, MUC1, and pS2, and by high iron diamine (HID) staining in 61 clinically confirmed IHACs. Results : MUC5AC (9/18, p0.05) displayed the most frequent expression in cholangiocarcinomas, and MUC2 (11/18, p0.05) was expressed more often in pancreatic adenocarcinomas than other IHAC, while MUC2 and 91.9H were not expressed at all in pancreatic adenocarcinomas. The positivity of several TRP did not correlate with tumor differentiation. Conclusions : MUC5AC, MUC2, mAb 91.9H, and HID may be useful in differentiating cholangiocarcinomas from colorectal adenocarcinomas.

Vasoactive Intestinal Peptide Induces MUC2/5AC Synthesis in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Vasointestinal peptide (VIP) is an important neurotransmitter involved in the regulation of mucus secretion, but the relationship of VIP and mucin genes is not clear. This study was designed to investigate the effect of VIP on MUC2/5AC genes expression and mucin secretion in human airway epithelial cells. MATERIALS AND METHOD: The mRNA levels of MUC2/5AC genes and mucin secretion were determined by RT-PCR and the immunoblot method in cultured human airway NCI-H292 epithelial cells. RESULTS: VIP (10-6-10-10 M) induced MUC2/5AC gene expression and mucin secretion in a reverse dose-dependant manner. The maximum expression of mRNA and mucin secretion level of MUC2/5AC was 10-10 M of VIP. Actinomycin D inhibited the VIP-mediated MUC2/5AC gene expression and mucin secretion, but cycloheximide did not. Budesonide attenuated the VIP-mediated MUC2/5AC genes expression and mucin secretion. RU-486, a glucocorticoid receptor antagonist, restored the inhibitory effect of budesonide. CONCLUSION: These results suggest that VIP regulates MUC2/5AC gene expression and secret mucin by transcriptional regulation, and that budesonide inhibits the VIP-mediated MUC2/5AC genes expression and mucin secretion through the glucocorticoid receptor.

MUC2/5AC Expression and Mucin Secretion through Leukotriene Receptor in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin production are highly increased during inflammatory airway disorders such as, asthma, chronic bronchitis and sinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators are related with secretion and production of mucin. However, among of inflammatory mediators, the relation of leukotrienes and mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC genes expression and mucin secretion through leukotriene receptor in human airway epithelial cells. SUBJECTS AND METHOD: The effect of Leukotriene D4 and leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion was observed in the human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS: Leukotriene D4 upregulated MUC2/5AC gene expression and mucin secretion on a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 micrometer) downregulated the leukotriene D4-mediated MUC2/5AC gene expression and mucin secretion. CONCLUSION: These results suggest that the leukotriene receptor system is one of the expression mechanisms of MUC2/5AC genes and mucin secretion.

Inhibitory effects on human gastric cancer cell line by MUC2 antisense oligodeoxynucleotide / 重庆医科大学学报

Objective:To investigate the inhibitory effect in vitro of mucin gene MUC2 antisense oligodeoxynucleotide (ASODN) on its gene expression and cell proliferation on gastric cancer cell line.Methods:Phosphorothioate MUC2 ASODN were synthesized and transfected to SGC7901 cells mediated by lipofectin.Their inhibitory effects on cell proliferation were determined by MTT method,light microscopy and immunohistochemical method.Results:The determination by MTT method demonstrated that MUC2 ASODN of varied concentrations could significantly inhibit the growth of SGC7901 cell lines while the control lipofectin showed no such effect.The result also suggested that the inhibitory effect was dose-dependent and time-dependent.The inhibition peaked at 48th hour after transfection,and the inhibition rate reached 55% when the concentration was 0.5?mol/L.After transfecting with MUC2 ASODN,SGC7901 cells showed decrease in number,volume and karyokinesis,increase in necroses under light microscopy.And the test by immunohistochemical method indicated that ASODN could downregulate the expression levels of MUC2 protein,MMP-2 protein and CD44V6 protein,but upregulate the expression levels of p16 protein.Conclusion:The data suggest that MUC2 ASODN transfection could effectively inhibit SGC7901 cells proliferation and invasion and metastasis potential of SGC7901 cells.

Effect of Beta Blocker on MUC2, MUC5AC Expression of the Cultured Human Conjunctival Cell

PURPOSE: To evaluate the characteristics of MUC2, MUC5AC expression and the effect of beta-blocker on MUC2, MUC5AC expression in cultured human conjunctival cell. METHODS: Human conjunctival cell was cultured. After obtaining the monoclonality of conjunctival cells, secondary culture was done. Cultured conjunctival cell was treated with 0.2 nM timolol. Specimen was collected in 1, 3, 5, 10 days after the confluence of cultured conjunctival cells. To determine the effect of beta blocker, Periodic acid-Schiff (PAS) staining, immunohistochemistry, RT-PCR, and flowcytometry were performed. RESULTS: Goblet cell was found in cultures of conjunctival cell. MUC5AC was detected in RT-PCR, immunohistochemistry, and flowcytometry, but MUC2 was detected only in flowcytometry. Beta blocker didn't have significant effects on expression of MUC2 and MUC5AC in flowcytometry. CONCLUSIONS: MUC2 and MUC5AC were detected in cultured conjunctival cell. Beta blocker may not affect goblet cell. The other factor will be related to goblet cell suppressing the mucin in long standing antiglaucomatous medication.

Effect of Macrolides on the Interleukin-1beta-mediated MUC2/5AC Genes Expression and Mucin Secretion in Human Airway Epithelial Cells

BACKGROUND AND OBJECTIVES: Macrolide is a relatively effective drug in chronic bronchiolitis and chronic sinusitis with mucous hypersecretion. However, the anti-secretory effect of macrolide is not clear. The aim of this study was to evaluate the effect of macrolide on the interleukin -1beta (IL-1beta)-induced MUC2/5AC genes expression and mucin secretion. Matrials and Methods: We observed effects of roxithromycin and clarithromycin on the IL-1beta-induced MUC2/5AC genes expression and mucin secretion in cultured human airway NCI-H292 epithelial cells. The steady state mRNA levels of MUC2/5AC and mucin secretion were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. RESULTS: Roxithromycin attenuated the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion. When roxithromycin treated before exposure to IL-1beta and after exposure to IL-1beta in cultured cells, both treatment methods inhibited the IL-1beta-induced MUC2/5AC genes expression and mucin secretion. However, clarithromycin did not suppress the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion. CONCLUSION: This result suggests that roxithromycin inhibits the IL-1beta-mediated mucin secretion through inhibition of MUC2/5AC genes expression.

Budesonide Down-regulates IL-1beta-Mediated MUC2/MUC5AC Genes Expression and Mucin Secretion in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucus hypersecretion is a hallmark of many respiratory inflammatory diseases such as asthma, bronchitis and sinusitis. While the current therapeutic pharmacological approaches to reducing mucus hypersecretion are limited, clinical studies have suggested that glucocorticoids reduce mucus secretion in patients with airway disease. However, the effect of glucocorticoids on mucus hypersecretion is not clear. Recently, we observed that IL-1beta induces MUC2 gene expression and mucin secretion in a previous experiment. This study was designed to investigate the effects of budesonide on the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion. MATERIALS AND METHOD: We observed the steady state mRNA level of MUC2/5AC genes using RT-PCR and mucin protein using immunoassay method in cultured human airway NCI-H292 epithelial cells. RESULTS: Budesonide attenuated IL-1beta-mediated MUC2/5AC gene expression as well as mucin secretion. The attenuated effect of budesonide was in a dose-dependent pattern. This attenuated effect of budesonide was blocked by glucocorticoid receptor antagonist, RU-486. CONCLUSION: This result suggests that budesonide suppresses the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion via blockage of glucocorticoid receptor.

Regulation of IL-1beta-Mediated MUC2 Gene and Mucin in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin secretion is regulated by the mucin genes (MUC) in the respiratory, gastrointestinal and reproductive system. Inflammation induces mucin hypersecretion in the human body. This study demonstrates the effects of IL-1beta on the regulation of mucin protein expression as well as the MUC2 gene in cultured airway epithelial cells. MATERIALS AND METHOD: Analysis of MUC2 gene was done by RT-PCR and the protein analysis was done by a flow cytometric analysis and an immunoassay method using cultured human airway epithelial cells, and NCI-H292 cells. RESULTS: The expression of MUC2 mRNA and protein induced by IL-1beta increased in a dose-and time-dependent manner. The maximum mRNA level of the MUC2 gene was approximately 3-fold, compared to that of the control cell. The IL-1beta-mediated MUC2 protein started at 6 hours of exposure to IL-1beta (20 ng/ml) and the maximum level was 12 hours. The MUC2 protein data of flow cytometric analysis corresponded to that of immunoassay analysis. The expression of MUC2 gene was suppressed by actinomycin D, but not attenuated by cycloheximide. CONCLUSION: These results suggest that the IL-1beta-mediated MUC2 gene and protein expression were increased in a dose- and time-dependent pattern and regulated by transcriptional step.