2.The Role of Gastric Acid in the H. pylori-induced Gastritis in Mouse.
Sung Soo KIM ; Yeo Min LEE ; Hyung Keun KIM ; Jin Il KIM ; Hiun Suk CHAE ; In Sik CHUNG ; Doo Ho PARK
The Korean Journal of Gastroenterology 2007;50(6):363-369
BACKGROUND/AIMS: This study was designed to investigate the role of gastric acid in the extent of H. pylori-induced gastritis. METHODS: Twenty eight mice were innoculated with live H. pylori. They were allocated into four groups. Mice in group I received no treatment, group II mice were treated with sham injection, group III received 125microgram/kg body weight of pentagastrin, while group IV received 250microgram/kg body weight of pentagastrin subcutaneously three times a week. After 7 months, the mucosal pH, H. pylori density, neutrophils and monocytes infiltration, and the degree of atrophy were assessed in the stomach. RESULTS: In the gastric body, the densities of H. pylori were not different among groups. The degree of neutrophil infiltration was significantly lower in group IV compared to other groups (p<0.05). The degree of monocyte infiltration was also significantly lower in group IV than group III (p<0.05). In the gastric antrum, there was no significant difference of the H. pylori density, neutrophil and monocyte infiltration, and degree of atrophy among the groups. The mice with the gastric mucosal pH lower than mean of 3.2 had significant lower level of H. pylori density (1.4 vs. 2.4, p=0.04), and infiltration of neutrophils (0.9 vs. 2.3, p=0.018), and monocytes (1.2 vs. 1.8; p=0.011) than the those with mucosal pH above 3.2 in the body of stomach. CONCLUSIONS: Gastric acid plays a role in suppressing the proximal propagation of H. pylori-induced gastritis to the body of stomach.
Animals
;
Female
;
Gastric Acid/*metabolism
;
Gastric Mucosa/pathology
;
Gastritis/immunology/*microbiology
;
Helicobacter Infections/*immunology/microbiology
;
*Helicobacter pylori/isolation & purification
;
Hydrogen-Ion Concentration
;
Mice
;
Mice, Inbred C57BL
;
Models, Animal
3.Gastric Autoantigenic Proteins in Helicobacter Pylori Infection.
Ji Sook PARK ; Su Jin LEE ; Tae Hyo KIM ; Jeongsuk YEOM ; Eun Sil PARK ; Ji Hyun SEO ; Jin Su JUN ; Jae Young LIM ; Chan Hoo PARK ; Hyang Ok WOO ; Hee Shang YOUN ; Gyung Hyuck KO ; Hyung Lyun KANG ; Seung Chul BAIK ; Woo Kon LEE ; Myung Je CHO ; Kwang Ho RHEE
Yonsei Medical Journal 2013;54(6):1342-1352
PURPOSE: This study tried to identify novel gastric autoimmune antigens that might be involved in aggravating the atrophic gastritis among patients with Helicobacter pylori infection using two-dimensional immunoblotting analysis. MATERIALS AND METHODS: Proteins from gastric mucosal antrectomy specimens and AGS cells (gastric adenocarcinoma cell lines derived from a Caucasian patient who had received no prior therapy) were 2-dimensionally immunoblotted separately with a pool of 300 sera from H. pylroi-infected patients at Gyeongsang National University Hospital. RESULTS: Thirty-eight autoantigenic proteins including alcohol dehydrogenase [NADP+], alpha enolase, gastrokine-1, gastric triacylglycerol lipase, heat shock 70 kDa protein 1, and peroxiredoxin-2 were identified in the gastric mucosal tissue. Fourteen autoantigenic proteins including programmed cell death 6-interacting protein, serum albumin and T-complex protein 1 subunit gamma were identified in the AGS cells. Albumin, alpha-enolase, annexin A3, cytoplasmic actin 1, heat shock cognate 71 kDa protein and leukocyte elastase inhibitor were commonly observed autoantigenic proteins in both gastric mucosal tissue and AGS cells. Alpha-enolase, glutathione S-transferase P, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1, human mitochondrial adenosine triphosphate synthase (ATP) subunit beta, mitochondrial 60 kDa heat shock protein, peroxiredoxin-2, 78 kDa glucose-regulated protein precursor, tyrosine-protein phosphatase non-receptor type 11 and Tryptophan-Aspartic acid (WD) repeat-containing protein 1 showed 60% or higher amino acid positivity. CONCLUSION: These newly identified gastric autoimmune antigens might be useful in the control and prevention of gastroduodenal disorders, and might be valuable in breaking the vicious circle that exists in gastroduodenal disorders if their pathophysiological roles could be understood in the progress of chronic atrophic gastritis, gastroduodenal ulcers, intestinal metaplasia, and gastric carcinogenesis.
Alcohol Dehydrogenase/metabolism
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Autoantigens/*metabolism
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Electrophoresis, Gel, Two-Dimensional
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Gastric Mucosa/metabolism/microbiology
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Helicobacter Infections/*metabolism
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Humans
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Peptide Hormones/metabolism
;
Phosphopyruvate Hydratase/metabolism
4.Usefulness of NCI-N87 Cell Lines in Helicobacter pylori Infected Gastric Mucosa Model.
Yong Jin JUNG ; Kook Lae LEE ; Byung Kwan KIM ; Ji Won KIM ; Ji Bong JEONG ; Sang Gyun KIM ; Joo Sung KIM ; Hyun Chae JUNG ; In Sung SONG
The Korean Journal of Gastroenterology 2006;47(5):357-362
BACKGROUND/AIMS: The unavailability of human gastric cell lines representative of the normal gastric epithelial function such as polarized monolayer restricts the application of cell culture system in approaching the field of Helicobacter pylori (H. pylori) infected gastric mucosa models. The present investigation aimed at assessing the usefulness of NCI-N87 cell line as an adequate cellular model to study the pathophysiology of human H. pylori infection. METHODS: For the identification of epithelial phenotypes at low magnification, cells were observed on a phase-contrast microscope and confocal microscope. Transepithelial resistance (TER) was measured on NCI-N87 cells seeded on Transwell(R) to identify monolayer polarity two or three times a week after confluency. The IL-8 level was determined by ELISA at 24 hours after the administration of HP60190 and IL-1alpha on NCI-N87 cells. IL-8 level was compared in both upper and lower well with the control. RESULTS: A monolayer phenotype was observed in NCI-N87 cell lines by using confocal microscope. TER was measured as 400-500 (omega x cm2) at two or three weeks after cell culture. In NCI-N87 cell lines, IL-8 level was significantly increased after 24 hour compared to control, and was prominent in the lower well. CONCLUSIONS: These results suggest that NCI-N87 cell line may be useful in H. pylori infected gastric mucosa model.
Cell Line
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Enzyme-Linked Immunosorbent Assay
;
Gastric Mucosa/*microbiology/pathology
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Helicobacter Infections/metabolism/*microbiology/pathology
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*Helicobacter pylori
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Humans
;
Interleukin-8/metabolism
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Microscopy, Confocal
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Microscopy, Phase-Contrast
;
Phenotype
5.The Relationship between Gastric Juice Nitrate/Nitrite Concentrations and Gastric Mucosal Surface pH.
Hae Kyung LEE ; Hyunjung KIM ; Hyung Keun KIM ; Young Seok CHO ; Byung Wook KIM ; Sok Won HAN ; Lee So MAENG ; Hiun Suk CHAE ; Hee Na KIM
Yonsei Medical Journal 2012;53(6):1154-1158
PURPOSE: To investigate gastric juice nitrate/nitrite concentration according to mucosal surface pH extent (area) of gastric corpus intimately contacting the gastric juice. MATERIALS AND METHODS: We included ninety-nine patients with dyspepsia. To evaluate gastric mucosal surface pH and its extent, gastric chromosocpy was performed by spraying phenol red dye on the corpus mucosa and estimating the extent of area with color changed. Nitrate/nitrite concentrations and pH of gastric juice were measured by ELISA and pH meter, respectively. Silver staining was done to histologically confirm the presence of Helicobacter pylori. RESULTS: Intragastric nitrate/nitrite concentrations in patients, showing phenol red staining mucosa were higher than those of unstaining mucosa (p=0.001): the more extensive in the area of phenol red staining area of corpus, the higher gastric juice pH found (r=0.692, p<0.001). Furthermore, the intragastric nitrate/nitrite concentrations correlated positively with gastric juice pH (r=0.481, p<0.001). CONCLUSION: The changes of mucosal surface pH and its extent in gastric corpus might affect either pH or nitrate/nitrite level of gastric juice.
Adult
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Aged
;
Dyspepsia/*metabolism/microbiology
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Enzyme-Linked Immunosorbent Assay
;
Female
;
Gastric Juice/*metabolism
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Gastric Mucosa/*metabolism/microbiology
;
Helicobacter pylori/isolation & purification
;
Humans
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Hydrogen-Ion Concentration
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Male
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Middle Aged
;
Nitrates/*metabolism
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Nitrites/*metabolism
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Young Adult
6.Protein expression and clinical significance of cyclooxygenase 2 and nuclear factor kappa B in gastric mucosa-associated lymphoid tissue lymphoma.
Xiu-Ling WU ; Shao-Liang HAN ; Li WAN ; Ka-Te HUANG
Chinese Journal of Gastrointestinal Surgery 2008;11(2):163-166
OBJECTIVETo investigate the protein expression of cyclooxygenase 2 (COX-2) and nuclear factor kappa B (NF-kappaB) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its clinical significance.
METHODSProtein expression of COX-2 and NF-kappaB in gastric MALT lymphoma were examined by immunohistochemistry of Envision two-step method. The correlations of COX-2 and NF-kappaB expression with Helicobacter pylori (Hp) infection, clinical stage, depth of tumor invasion, tumor size, recurrent rate and treatment were analyzed by univariate, multivariate and Pearson analysis.
RESULTSThe positive expression of COX-2 and NF-kappaB in gastric MALT lymphoma were 48.9%(23/47) and 36.2% (17/47) respectively, and a positive correlation was found between these two factors(r=0.326,P<0.05). Moreover, COX-2 expression was positively correlated with Hp infection,clinical stage, depth of invasion and tumor size (P<0.05). Univariate analysis showed that the overall survival of gastric MALT lymphoma patients with positive COX-2 protein (59.9 months) was shorter than that of patients with negative COX-2 protein (77.8 months), but the difference was not significant (P>0.05). The survival was significantly shorter in gastric MALT lymphoma patients with positive NF-kappaB protein (26 months) than that of patients with negative NF-kappaB protein (123.2 months)(P<0.05). Multivariate Cox regression analysis revealed that clinicopathological stage was independent prognostic factor, and associated with short survival.
CONCLUSIONUp-regulated expression of COX-2 and activation of NF-kappaB are associated with Hp infection in gastric MALT lymphoma, and their protein expression is correlated with the development of tumor and prognosis.
Cyclooxygenase 2 ; metabolism ; Female ; Gastric Mucosa ; metabolism ; microbiology ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Humans ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; microbiology ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; metabolism ; microbiology ; pathology
7.Glutathione Levels in Helicobacter pylori-infected Gastric Mucosa.
Dong Kyun PARK ; Seung Ki JEONG ; Moon Gi CHUNG ; Oh Sang KWON ; Sun Suck KIM ; Yang Suh KOO ; Yu Kyung KIM ; Yeon Suk KIM ; Duck Joo CHOI ; Chang Shin PARK ; Woon Gye CHUNG ; Ju Hyun KIM
The Korean Journal of Gastroenterology 2003;42(4):267-273
BACKGROUND/AIMS: Oxidative stress may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori (H. pylori). H. pylori induces recruitment and activation of inflammatory cells, which produces reactive oxygen species. H. pylori extract directly induces the synthesis of reactive oxygen species in gastric epithelial cells and causes DNA damage. The aim of this study was to investigate the association between the levels of glutathione (GSH) and H. pylori density, histological findings, endoscopic findings, clinical variables, and virulence factors. METHODS: Gastric biopsy specimens were obtained from 73 consecutive patients. The 5,5'-dithiobis-(2-nitrobenzoic acid) reaction was used to determine GSH levels. RESULTS: The infection rate of H. pylori was 68.5%. The GSH level was not related to age, sex, alcohol intake, and endoscopic findings. The GSH level was lower in patients infected with H. pylori. GSH levels were not correlated significantly with the grades of neutrophil, intestinal metaplasia, and atrophy. However, the GSH levels were significantly correlated with H. pylori density (r=-0.296, p=0.01) and monocyte grade (r=-0.257, p=0.02). The GSH levels were not related to CagA, VacA, and UreA. CONCLUSIONS: This study suggests that H. pylori causes oxidative stresses which deplete GSH in gastric mucosa of patients infected with H. pylori.
Adolescent
;
Adult
;
Aged
;
Female
;
Gastric Mucosa/*metabolism/pathology
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Glutathione/*metabolism
;
Helicobacter Infections/*metabolism/pathology
;
*Helicobacter pylori
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Humans
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Male
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Middle Aged
;
Oxidative Stress
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Stomach Diseases/*metabolism/microbiology/pathology
8.Glutathione Levels in Helicobacter pylori-infected Gastric Mucosa.
Dong Kyun PARK ; Seung Ki JEONG ; Moon Gi CHUNG ; Oh Sang KWON ; Sun Suck KIM ; Yang Suh KOO ; Yu Kyung KIM ; Yeon Suk KIM ; Duck Joo CHOI ; Chang Shin PARK ; Woon Gye CHUNG ; Ju Hyun KIM
The Korean Journal of Gastroenterology 2003;42(4):267-273
BACKGROUND/AIMS: Oxidative stress may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori (H. pylori). H. pylori induces recruitment and activation of inflammatory cells, which produces reactive oxygen species. H. pylori extract directly induces the synthesis of reactive oxygen species in gastric epithelial cells and causes DNA damage. The aim of this study was to investigate the association between the levels of glutathione (GSH) and H. pylori density, histological findings, endoscopic findings, clinical variables, and virulence factors. METHODS: Gastric biopsy specimens were obtained from 73 consecutive patients. The 5,5'-dithiobis-(2-nitrobenzoic acid) reaction was used to determine GSH levels. RESULTS: The infection rate of H. pylori was 68.5%. The GSH level was not related to age, sex, alcohol intake, and endoscopic findings. The GSH level was lower in patients infected with H. pylori. GSH levels were not correlated significantly with the grades of neutrophil, intestinal metaplasia, and atrophy. However, the GSH levels were significantly correlated with H. pylori density (r=-0.296, p=0.01) and monocyte grade (r=-0.257, p=0.02). The GSH levels were not related to CagA, VacA, and UreA. CONCLUSIONS: This study suggests that H. pylori causes oxidative stresses which deplete GSH in gastric mucosa of patients infected with H. pylori.
Adolescent
;
Adult
;
Aged
;
Female
;
Gastric Mucosa/*metabolism/pathology
;
Glutathione/*metabolism
;
Helicobacter Infections/*metabolism/pathology
;
*Helicobacter pylori
;
Humans
;
Male
;
Middle Aged
;
Oxidative Stress
;
Stomach Diseases/*metabolism/microbiology/pathology
9.The Effect of Rosiglitazone on the Cell Proliferation and the Expressions of p27 and Skp2 in Helicobacter pylori Infected Human Gastric Epithelial Cells.
Sung Soo KIM ; Young Seok CHO ; Hyung Keun KIM ; Ok Ran SHIN ; Hiun Suk CHAE ; Myung Gyu CHOI ; In Sik CHUNG
The Korean Journal of Gastroenterology 2010;55(4):225-231
BACKGROUND/AIMS: Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the ligand-activated nuclear receptor superfamily, exhibit anti-tumoral effects and are associated with de novo synthesis of proteins involved in regulating the cell cycle and cell survival/death. Helicobacter pylori (H. pylori) is an etiologic agent for gastric adenocarcinoma, and raises the cell turnover of gastric epithelium. The aim of this study was to investigate the effect of PPAR gamma ligand rosiglitazone on the cell proliferation and the expressions of p27 and Skp2 protein in H. pylori infected gastric epithelial cells. METHODS: We examined the expression of PPAR gamma by Western blot in H. pylori infected AGS human gastric epithelial cells. The effect of rosiglitazone on the survival of H. pylori infected AGS cells was assessed by cell viability assay. After the treatment of rosiglitazone in H. pylori infected AGS cells, the expressions of p27 and Skp2 were assessed by Western blot. RESULTS: The expression of PPAR gamma protein was increased in H. pylori infected AGS cells. Cell growth was inhibited and decreased in dose- and time- dependent manner in H. pylori infected AGS cells treated with rosiglitazone. A decrease in Skp2 expression and a reciprocal increase in p27 expression were found in dose- and time-dependent manner in H. pylori infected AGS cells treated with rosiglitazone. CONCLUSIONS: Rosiglitazone inhibited the growth of H. pylori infected AGS cells. Rosiglitazone attenuated Skp2 expression, thereby promoting p27 accumulation in H. pylori infected human gastric epithelial cells. Further studies will be needed to find the effects of accumulation on cell turnover in H. pylori infection and the role in the H. pylori-associated gastric carcinogenesis.
Anti-Bacterial Agents/*pharmacology
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Cell Line
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p27/*metabolism
;
Epithelial Cells/metabolism/*microbiology
;
Gastric Mucosa/cytology/metabolism/*microbiology
;
*Helicobacter pylori
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Humans
;
PPAR gamma/antagonists &inhibitors/metabolism
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S-Phase Kinase-Associated Proteins/*metabolism
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Thiazolidinediones/*pharmacology
10.Expression of gastrin, somatostatin, PCNA and Fas-L in the mucosa of gastric antrum of children with chronic gastritis and duodenal ulcer.
Xiao-zhi XIE ; Zong-min WANG ; Hai-yan ZHANG ; Lan WANG ; Bao-hui GAO ; Xue-mei LI ; Wei-guo HU
Chinese Journal of Pediatrics 2006;44(10):774-777
OBJECTIVESince application of pediatric gastroscopy in the mid-nineteen nineties, there has been a trend that the prevalence rates of pediatric gastritis and duodenal ulcer (DU) are increasing. The diagnosed rate of pediatric gastritis has accounted for 85% - 95% of the total number of children who received gastroscopy, and the rate of DU accounted for 8% - 22%. Such a high rates of the diseases may influence the development of the children severely. However, the etiology and pathogenesis of pediatric chronic gastritis and DU have not been completely elucidated. The disordered gastrointestinal hormones play a crucial role in the pediatric chronic gastritis and DU. This study focused on the expression of gastrin (GAS), somatostatin (SS) in the mucosa of gastric antrum and PCNA and Fas-L in the sinus ventriculi and their possible roles in the pathogenesis of pediatric chronic gastritis and DU.
METHODThe sinus ventriculi mucosal samples of 83 cases were collected via gastroscopic biopsy from the hospital during the recent two years and the cases were divided into five groups: group A, chronic superficial gastritis, Helicobacter pylori (Hp)(+); group B, chronic superficial gastritis, Hp(-); group C, DU, Hp(+); Group D, DU, Hp(-); Group E, normal sinus ventriculi mucosa, Hp(-). Immunohistochemical staining (En Vision) was carried out for GAS, SS, PCNA and Fas-L, and positive cells of each slide were counted (x 400). Statistically significant differences among groups for continuous data were assessed with the software SPSS10.0.
RESULTSThe expressions of GAS and SS in the groups A through E had no significant difference. The expression of PCNA in group A was significantly higher than that in group B (P < 0.05), and no significant differences were found among the other groups. There were no significant differences in expressions of Fas-L among the five groups.
CONCLUSIONThere seems to be an increasing tendency in the expressions of GAS and SS in children with chronic gastritis and duodenal ulcer. Hp infection promotes the multiplication of the sinus ventriculi mucosal epithelium cells in the pediatric chronic gastritis.
Adolescent ; Biopsy ; Child ; Child, Preschool ; Duodenal Ulcer ; metabolism ; microbiology ; pathology ; Fas Ligand Protein ; metabolism ; Female ; Gastric Mucosa ; metabolism ; pathology ; Gastrins ; metabolism ; Gastritis ; metabolism ; microbiology ; pathology ; Gastroscopy ; Helicobacter Infections ; microbiology ; Helicobacter pylori ; isolation & purification ; pathogenicity ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Proliferating Cell Nuclear Antigen ; metabolism ; Pyloric Antrum ; metabolism ; pathology ; Somatostatin ; metabolism