1.Tumor infiltrating dendritic cells and Mucin1 gene expression in benign prostatic hyperplasia and prostate cancer.
Song-Tao XIANG ; Si-Wei ZHOU ; Wei GUAN ; Qin-Zhang WANG ; Bao ZHANG ; Ji-Hong LIU ; Zhang-Qun YE
National Journal of Andrology 2003;9(7):497-500
OBJECTIVETo study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer.
METHODSMucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method.
RESULTSMUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001).
CONCLUSIONSThe expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.
Antigens, Neoplasm ; biosynthesis ; Dendritic Cells ; immunology ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Mucin-1 ; Mucins ; biosynthesis ; Prostatic Hyperplasia ; immunology ; metabolism ; pathology ; Prostatic Neoplasms ; immunology ; metabolism ; pathology
2.Effects of glucocorticoid on IL-13-induced Muc5ac expression in airways of mice.
Jianbo, LIU ; Zhenxiang, ZHANG ; Yongjian, XU ; Lihua, XING ; Huilan, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(6):575-7
To study the effects of glucocorticoid on the IL-13-induced Muc5ac expression in airways of mice, and investigate its role in mucus secretion of airways, 24 pathogen-free BALB/c mice were randomly divided into 3 groups. IL-13 group received an nasal instillation of 100 microg of recombinant murine IL-13 solution on days 1, 3 and 5. In dexamethasone group, dexamethasone (0.5 mg/kg) was administered intraperitoneally 24 h before and 1 h before the first instillation of IL-13 and on 4 consecutive days (day 0 to day 5, 6 consecutive days in total), while control group was not treated with IL-13 or dexamethasone. Bronchoalveolar lavage fluid (BALF) was collected and eosinophils were counted, and expression of Muc5ac mRNA and protein in lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) technology and immunohistochemical assay respectively. Our results showed that the number of mice, with positve Muc5ac protein expression, expression of Muc5ac mRNA and eosinophils in BALF after IL-13 treatment were all significantly higher than that of control group (all P<0.01). Despite eosinophils reduced (P<0.01), the number of mice with positive Muc5ac protein expression, expression of Muc5ac mRNA afterdexamethasone treatment didn't decreas significantly as compared with that of IL-13 group. It is concluded that IL-13 can up-regulate the expression of Muc5ac mRNA and protein, which may play a pivotal role in the mucus overproduction of airways. Dexamethasone can suppress IL-13-induced eosinophilic infiltration in lung but can't inhibit the mucus overproduction.
Bronchoalveolar Lavage Fluid/cytology
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Dexamethasone/*pharmacology
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Interleukin-13/*pharmacology
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Mice, Inbred BALB C
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Mucins/*biosynthesis
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Mucins/genetics
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Mucus/secretion
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RNA, Messenger/biosynthesis
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RNA, Messenger/genetics
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Random Allocation
;
Respiratory System/*metabolism
3.Clinical significance of the expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients.
Xiao-hui LI ; Jiong-xin XIONG ; Chun-you WANG
Acta Academiae Medicinae Sinicae 2005;27(5):624-627
OBJECTIVETo explore the expression and clinical significance of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients.
METHODSThe expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients were detected with reverse transcription realtime PCR.
RESULTSExpression of MUC4 mRNA was not detected in the peripheral blood mononuclear cells of chronic pancreatitis patients and normal healthy people, but was observed in those of pancreatic cancer patients. The positive expression rate of MUC4 mRNA in pancreatic cancer patients was 60%, which was significantly higher than those of chronic pancreatitis patients and normal healthy people (P < 0.01). The positive expression rate of MUC4 mRNA increased with the development of clinical stage, and the positive expression rate in stage of II - IV (TNM system) was 76.92%, which was significantly higher than that of I - II stage (P < 0.01).
CONCLUSIONSExpression of MUC4 mRNA is highly correlated with the clinical stage in pancreatic cancer patients. Detecting the expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients may be helpful for the early diagnosis and differential diagnosis.
Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Female ; Humans ; Male ; Middle Aged ; Monocytes ; metabolism ; Mucins ; biosynthesis ; genetics ; Neoplasm Staging ; Pancreatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction
4.Coexpression of MUC1 with p53 or MUC2 correlates with Lymph Node Metastasis in Colorectal Carcinomas.
Kee Taek JANG ; Seoung Wan CHAE ; Jin Hee SOHN ; Hye Rim PARK ; Hyung Sik SHIN
Journal of Korean Medical Science 2002;17(1):29-33
The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.
Adult
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Aged
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Aged, 80 and over
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Colorectal Neoplasms/*metabolism/pathology
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Female
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Humans
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Lymph Nodes
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Lymphatic Metastasis
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Male
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Middle Aged
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Mucin-1/*biosynthesis
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Mucin-2
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Mucins/*biosynthesis
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Tumor Suppressor Protein p53/*biosynthesis
5.Neutrophil Elastase Causes MUC5AC Mucin Synthesis Via EGF Receptor, ERK and NF-kB Pathways in A549 Cells.
Jeong Sup SONG ; Kyung Sook CHO ; Hyung Kyu YOON ; Hwa Sik MOON ; Sung Hak PARK
The Korean Journal of Internal Medicine 2005;20(4):275-283
BACKGROUND: Neutrophil elastase (NE) was found to increase the respiratory mucin gene, MUC5AC, although the molecular mechanisms of this process remain unknown. We attempted to determine the signal transduction pathway through which NE induces MUC5AC gene expression in bronchial epithelial cells. METHODS: A fragment of 1.3 Kb MUC5AC promoter which had been cloned into the pGL3-Basic luciferase vector was transfected to the A549 cells. By measuring the luciferase activity, we were able to evaluate the MUC5AC promoter activity in A549 cells. The involvement of mitogen-activated protein kinases (MAPK) was confirmed by Western blotting. To confirm the involvement of nuclear factor kappaB (NF-kB), we used site-directed mutagenesis and electrophoretic mobility shift assay (EMSA) autoradiogram. The MUC5AC mRNA expression was confirmed by RT-PCR. RESULTS: NE increased the transcriptional activity of the MUC5AC promoter in A549 cells. The increased transcriptional activity of the MUC5AC promoter by NE was found to be associated with increased NF-kB activity. Site-directed mutagenesis showed that the transfection of the mutated NF-kB binding sites from the PGL3-MUC5AC-3752 promoter luciferase reporter plasmid decreased the luciferase activity after NE stimulation. Among the MAPKs, only extracellular signal-regulated kinases (ERK) were involved in this NE-induced MUC5AC mucin expression. RT-PCR also showed that NE increased MUC5AC mRNA. An EMSA autoradiogram revealed that NE induced NF-kB: DNA binding. CONCLUSIONS: These results indicate that human NE induces MUC5AC mucin through the epidermal growth factor receptor (EGF-R), ERK, and NF-kB pathways in A549 cells.
Transcription, Genetic
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Signal Transduction
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Receptor, Epidermal Growth Factor/*metabolism
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NF-kappa B/*metabolism
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Mucins/*biosynthesis/genetics
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Leukocyte Elastase/*metabolism
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Humans
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Gene Expression Regulation
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Extracellular Signal-Regulated MAP Kinases/*metabolism
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Epithelial Cells
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Cell Line, Tumor
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Bronchi/cytology
6.Effects of glucocorticoid on IL-13-induced Muc5ac expression in airways of mice.
Jianbo LIU ; Zhenxiang ZHANG ; Yongjian XU ; Lihua XING ; Huilan ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(6):575-577
To study the effects of glucocorticoid on the IL-13-induced Muc5ac expression in airways of mice, and investigate its role in mucus secretion of airways, 24 pathogen-free BALB/c mice were randomly divided into 3 groups. IL-13 group received an nasal instillation of 100 microg of recombinant murine IL-13 solution on days 1, 3 and 5. In dexamethasone group, dexamethasone (0.5 mg/kg) was administered intraperitoneally 24 h before and 1 h before the first instillation of IL-13 and on 4 consecutive days (day 0 to day 5, 6 consecutive days in total), while control group was not treated with IL-13 or dexamethasone. Bronchoalveolar lavage fluid (BALF) was collected and eosinophils were counted, and expression of Muc5ac mRNA and protein in lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) technology and immunohistochemical assay respectively. Our results showed that the number of mice, with positve Muc5ac protein expression, expression of Muc5ac mRNA and eosinophils in BALF after IL-13 treatment were all significantly higher than that of control group (all P<0.01). Despite eosinophils reduced (P<0.01), the number of mice with positive Muc5ac protein expression, expression of Muc5ac mRNA afterdexamethasone treatment didn't decreas significantly as compared with that of IL-13 group. It is concluded that IL-13 can up-regulate the expression of Muc5ac mRNA and protein, which may play a pivotal role in the mucus overproduction of airways. Dexamethasone can suppress IL-13-induced eosinophilic infiltration in lung but can't inhibit the mucus overproduction.
Animals
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Bronchoalveolar Lavage Fluid
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cytology
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Dexamethasone
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pharmacology
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Interleukin-13
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pharmacology
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Male
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Mice
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Mice, Inbred BALB C
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Mucin 5AC
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Mucins
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biosynthesis
;
genetics
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Mucus
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secretion
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RNA, Messenger
;
biosynthesis
;
genetics
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Random Allocation
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Respiratory System
;
metabolism
7.MUC5AC expression up-regulation goblet cell hyperplasia in the airway of patients with chronic obstructive pulmonary disease.
Rui MA ; Ying WANG ; Gang CHENG ; Hui-Zhen ZHANG ; Huan-Ying WAN ; Shao-Guang HUANG
Chinese Medical Sciences Journal 2005;20(3):181-184
OBJECTIVETo determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pulmonary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function.
METHODSEighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the expression of MUC5AC in the paraffin's section was tested by immunohistochemistry.
RESULTSGoblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% +/- 0.10%) was significantly higher than that in the normal lung function group (0.13% +/- 0.06%, P < 0.05). The positive rate of MUC5AC expression in the COPD group (0.27% +/- 0.09%) was higher than that in the normal lung function group (0.20% +/- 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% +/- 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% +/- 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% +/- 6.44% and 10.88% +/- 7.10%, respectively).
CONCLUSIONFor COPD patients with declined lung function, there were goblet cell hyperplasia and increased expression of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.
Aged ; Bronchi ; pathology ; Cell Proliferation ; Epithelium ; pathology ; Exocrine Glands ; metabolism ; Goblet Cells ; pathology ; Humans ; Hyperplasia ; Middle Aged ; Mucin 5AC ; Mucins ; biosynthesis ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Smoking ; Up-Regulation
8.Therapeutic effects of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers.
Bing ZHOU ; Jia-bang LI ; Guang-xian CAI ; Jiang-hong LING ; Xing-ping DAI
Journal of Central South University(Medical Sciences) 2005;30(6):714-718
OBJECTIVE:
To explore the therapeutic effects and mechanisms of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers.
METHODS:
One hundred and twenty patients were randomly divided into 6 groups. Another 10 patients as the control group were confirmed with no peptic ulcers by endoscope, but had digestive tract symptoms. The clinical effects were compared among each group after the one month treatment.
RESULTS:
The clinical effects of the combination of Jianweiyuyang granules and ranitidine capsules were better than those of western medicine, with improvement in symptoms and syndrome (P < 0.01 to 0.05), but there was not significant difference with the rate of ulcer healing and the Hp clearance among the combination of Jianweiyuyang granules and ranitidine capsules, Jianweiyuyang granules, and ranitidine capsules (P > 0.05). The combination of Jianweiyuyang granules and ranitidine capsules could significantly upregulate the expression of MUCSAC mRNA (P < 0.01), while downregulate the expression of ETAR mRNA (P < 0.01).
CONCLUSION
There is obvious advantage in treating peptic ulcers by the combination of Jianweiyuyang granules and ranitidine capsules, and its mechanisms may be to protect the gastric mucosal barrier by up-regulating the expression of MUCSAC mRNA and to improve the gastric mucosal blood flow by down-regulating the expression of ETAR mRNA.
Adult
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Capsules
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Drug Therapy, Combination
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Drugs, Chinese Herbal
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therapeutic use
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Endothelin-1
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biosynthesis
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genetics
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Female
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Gastric Mucosa
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metabolism
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Humans
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Male
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Middle Aged
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Mucin 5AC
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Mucins
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biosynthesis
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genetics
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Peptic Ulcer
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drug therapy
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Phytotherapy
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RNA, Messenger
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biosynthesis
;
genetics
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Ranitidine
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therapeutic use
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Receptors, Endothelin
;
biosynthesis
;
genetics
9.Interleukin-1 beta Induces MUC2 Gene Expression and Mucin Secretion via Activation of PKC-MEK/ERK,and PI3K in Human Airway Epithelial Cells.
Yong Dae KIM ; Jae Yun JEON ; Hyun Jae WOO ; Jung Cheul LEE ; Jin Hong CHUNG ; Si Youn SONG ; Seok Keun YOON ; Suk Hwan BAEK
Journal of Korean Medical Science 2002;17(6):765-771
Interleukin 1 beta (IL-1 beta), a proinflammatory cytokine, is related with inflammatory diseases and it up-regulates MUC2 gene expression and mucin secretion. This study was designed to investigate the signal transduction pathway of the IL-1 beta-mediated MUC2 gene expression and mucin secretion in human airway epithelial cells. In cultured human airway NCI-H292 epithelial cells, the steady state of the mRNA level of MUC2 gene expression and mucin secretion induced by IL-1 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunoblot analysis. To observe the signal pathway of the IL-1 beta-mediated MUC2 gene expression and mucin secretion, we used several specific inhibitors. PD98059 (MEK/ERK inhibitor) suppressed IL-1 beta-mediated MUC2 gene expression and mucin secretion, while SB203580 (p38 inhibitor) did not. Ro31-8220 (PKC inhibitor) inhibited IL-1 beta-mediated MUC2 gene expression and mucin secretion. It inhibited ERK phosphorylation, but did not inhibit p38 phosphorylation. LY294002 (PI3K inhibitor) also suppressed MUC2 expression, but did not inhibit any MAPKs phosphorylation. These results suggest that the IL-1 -mediated MUC2 gene expression and mucin secretion in NCI-H292 cells are regulated through activation of the PKC-MEK/ERK pathway, and that PI3K is also involved in the IL-1 beta-mediated MUC2 gene expression and mucin secretion.
1-Phosphatidylinositol 3-Kinase/*metabolism
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Cell Line
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Chromones/pharmacology
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Dose-Response Relationship, Drug
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Enzyme Activation
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Enzyme Inhibitors/pharmacology
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Epithelium/*enzymology
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Flavonoids/pharmacology
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Humans
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Imidazoles/pharmacology
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Immunoassay
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Immunoblotting
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Indoles/pharmacology
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Interleukin-1/metabolism/*physiology
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Lung/cytology/*metabolism
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MAP Kinase Signaling System
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Mitogen-Activated Protein Kinase Kinases/*metabolism
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Morpholines/pharmacology
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Mucin-2
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Mucins/*biosynthesis/metabolism
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Phosphorylation
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Protein Kinase C/*metabolism
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Protein Structure, Tertiary
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Pyridines/pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Time Factors