1.Helicobacter pylori in Human Stomach: Can It Be Called Mutualism or a Disease?.
The Korean Journal of Gastroenterology 2012;59(5):329-337
Helicobacter pylori (H. pylori) has been a major concern as a gastric pathogen with unique features since discovered in the end of the 20th century. Recent data on comparative genome study have revealed that H. pylori has successfully survived with its host though over 58,000 years of evolution and migration from continent to continent. To maintain the symbiotic relationship with human, H. pylori has come up with ways to induce host tolerance as well as exert harmful injuries. Studies about H. pylori have accumulated the knowledge about how the cellular and molecular interactions are controlled and regulated to decide whether the symbiotic relationship is directed to diseases or peaceful mutualism. We reviewed recent literatures and research outcomes about the H. pylori and host interaction in molecular and cellular basis.
Adaptive Immunity
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Epithelial Cells/metabolism/microbiology/pathology
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Helicobacter Infections/immunology/metabolism/*pathology
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Helicobacter pylori/*immunology
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*Host-Pathogen Interactions
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Humans
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Symbiosis
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T-Lymphocytes/immunology/metabolism
2.The Change of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in the Gastric Mucosa One Year after Eradication of Helicobacter pylori.
Sung Soo KIM ; Young Jick SUNG ; Min Kyoung PARK ; Chang Hoon LIM ; Hong Jun YANG ; Tae Ho KIM ; Chang Whan KIM ; Jin Il KIM ; Sok Won HAN ; In Sik CHUNG
The Korean Journal of Gastroenterology 2008;52(5):286-292
BACKGROUND/AIMS: The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), the proteins that have the role in the gastric carcinogenesis, are stimulated by H. pylori infection in the gastric mucosa. The aim of this study was to evaluate the expression of COX-2 and iNOS proteins one year after the eradication of H. pylori. METHODS: Gastric antral mucosa from fifty eight patients with chronic gastritis who were all infected with H. pylori was examined for the expression of COX-2 and iNOS proteins before and one year after the eradication of H. pylori by immunohistochemical stain. RESULTS: COX-2 and iNOS proteins were expressed in the epithelial cells and interstitial inflammatory cells of gastric mucosa. Percent expressions of COX-2 and iNOS were significantly decreased one year after the eradication in the patients with cured infection, but not in those having persistent H. pylori. COX-2 and iNOS expressions were well correlated with H. pylori density, acute and chronic inflammation of gastric mucosa. CONCLUSIONS: The eradication of H. pylori can decrease the expression of COX-2 and iNOS in the gastric mucosa in long-term period. This seems to be due to the removal of H. pylori itself and related regression of gastric inflammation.
Cyclooxygenase 2/immunology/*metabolism
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Drug Therapy, Combination
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Gastric Mucosa/*enzymology
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Helicobacter Infections/drug therapy
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*Helicobacter pylori
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Humans
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Nitric Oxide Synthase Type II/immunology/*metabolism
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Time Factors
3.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
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Female
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Gastric Acid/*metabolism
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Gastric Mucosa/pathology
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Gastritis/immunology/*microbiology
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Helicobacter Infections/*immunology/microbiology
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*Helicobacter pylori/isolation & purification
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Hydrogen-Ion Concentration
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Mice
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Mice, Inbred C57BL
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Models, Animal
4.Expression of Mucosal Cyto-Chemokine mRNAs in Patients with Helicobacter pylori Infection.
Sill Moo PARK ; Jin Hee KIM ; Yo Han HONG ; Hye Ryung JUNG ; Joongwon PARK ; Jae Gyu KIM ; Bung Chul YOO
The Korean Journal of Internal Medicine 2001;16(4):230-235
BACKGROUND: Helicobacter pylori-induced destruction of the gastroduodenal mucosal barrier is initiated with mucosal infiltration of inflammatory cells. Cytokines and chemokines have been suggested to play important roles in the migration and activation of these inflammatory cells into the mucosa. The present study aimed to investigate expression rates of cyto-chemokine mRNAs using gastric mucosal biopsy specimens. METHODS: In 98 patients infected with Helicobacter pylori, mucosal mRNA expression rates of cytokines (IL-1beta, IL-6, and IL-10), C-C chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], and macrophage inflammatory protein 1beta [MIP-1beta], monocyte chemotactic and activating factor [MCAF], regulated on activation, normal T cell expressed and presumably secreted [RANTES]) and C-X-C chemokines (IL-8 and growth regulated alpha [GRO-alpha]) were examined using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression rates of mRNA for IL-8, GRO-alpha, MIP-1alpha and RANTES were significantly more increased in H. pylori-positive patients than in H. pylori- negative patients. However, the expressions of IL-1beta, IL-6 and IL-10 mRNA were statistically not different between two groups. After eradication of H. pylori, expressions of mRNA for three cytokines (IL-1beta, IL-6 and IL-10), four C-C chemokines (MIP-1alpha, MIP-1beta, MCAF and RANTES) and two C-X-C chemokines (IL-8 and GRO-alpha) were significantly decreased. CONCLUSION: These results suggest that C-X-C chemokines and some C-C chemokines play important roles in H. pylori-associated peptic ulcer diseases.
Adult
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Aged
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Aged, 80 and over
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Chemokines, CC/metabolism
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Chemokines, CXC/metabolism
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Chi-Square Distribution
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Cytokines/*metabolism
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Female
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Gastric Mucosa/*immunology/metabolism
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Helicobacter Infections/*immunology/metabolism
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*Helicobacter pylori
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Human
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Male
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Middle Age
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Prospective Studies
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RNA, Messenger/metabolism
5.A Study of Oxidative Stress Parameters in Anti-Helicobacter Pylorus Immunoglobulin G Positive and Negative Gastric Cancer Patients.
Tevfik NOYAN ; Huseyin GUDUCUOGLU ; Mahmut ILHAN
Yonsei Medical Journal 2009;50(5):677-682
PURPOSE: Helicobacter pylorus (HP) is a Gram-negative spiral-shaped microaerophilic bacterium, which colonizes in the gastric mucosa of humans. The gastric human pathogen HP causes chronic gastritis and ulcers, and has a strong relationship with gastric cancer. The aim of this study was to determine advanced oxidation protein products (AOPP) levels, activities of myeloperoxidase (MPO) and catalase (CAT) in two groups. MATERIALS AND METHODS: For this aim, one group included 30 patients with gastric cancer (Group 1) and the other included 30 subjects with non-gastric cancer and Anti-HP immunoglobulin (Ig) G antibody positive (group 2). Anti-HP IgG antibody test values were found as positive in fifty percent of group 1 and all of the group 2 patients. RESULTS: Significantly increased AOOP levels were found in group 1 (p < 0.05) compared to group 2. There were no significant differences between the groups in regard to activities of MPO and CAT. In addition, AOPP level, MPO and CAT activities were similar among the Anti-HP IgG positive and negative subgroups of group 1 patients. CONCLUSION: The result of this study indicated that gastric cancer patients were characterized by increased protein oxidation, whereas there was no significant difference in oxidative stress parameters and antioxidant enzyme activity between the Anti-HP IgG positive and negative gastric cancer patients.
Adult
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Aged
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Catalase/blood
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Female
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Helicobacter Infections/*immunology/metabolism
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Helicobacter pylori/*immunology
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Humans
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Immunoglobulin G/*blood
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Male
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Middle Aged
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Oxidation-Reduction
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*Oxidative Stress
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Peroxidase/blood
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Stomach Neoplasms/blood/immunology/*metabolism
6.Construction of a recombinant Lactobacillus acidophilus expressing high levels of Helicobacter pylori adhesin Hp0410.
Li-fang ZHU ; Bei-guo LONG ; Jun LUO ; Rong JIANG ; Hong-ying FANG
Journal of Southern Medical University 2010;30(2):334-337
OBJECTIVETo construct a recombinant Lactobacillus acidophilus that expresses high levels of Helicobacter pylori (Hp) adhesin Hp0410.
METHODSThe gene fragment encoding Hp0410 was amplified by PCR from the DNA of H. pylori NCTC11639 strain and cloned into the shuttle plasmid pMG36e to construct pMG36e-Hp0410, which was transformed into Lactobacillus acidophilus by electroporation. The target protein was confirmed with SDS-PAGE and silver nitrate staining and analyzed by Western blotting. The stability of the recombinant plasmid was assessed by drawing the growth curve of the recombinant Lactobacillus acidophilus.
RESULTSA 750-bp fragment was inserted into the pMG36e plasmid and transformed into Lactobacillus lactis. The transformed bacterium expressed the target protein with a relative molecular mass of about 34 kD. Western blotting confirmed that the expressed proteins could be recognized by the serum of patients with Hp infection. The recombinant plasmid pMG36e-Hp0410 exhibited good stability in the presence or absence of erythromycin.
CONCLUSIONSThe recombinant Lactobacillus acidophilus with high constitutive expression of Hp0410 has been constructed successfully.
Adhesins, Bacterial ; biosynthesis ; genetics ; immunology ; Bacterial Vaccines ; biosynthesis ; Helicobacter Infections ; prevention & control ; Humans ; Lactobacillus acidophilus ; genetics ; metabolism ; Plasmids ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; Vaccines, Attenuated ; biosynthesis
7.Oral immunization of mice with vaccine of attenuated Salmonella typhimurium expressing Helicobacter pylori urease B subunit.
Xing-Long YANG ; Wen-Chao LIU ; Wu-Wei YANG ; Dong ZHONG ; Yu-Hu LIU ; Jing-Dong ZHANG ; Jian-Hui JIANG ; Shan-Shan LI
Biomedical and Environmental Sciences 2005;18(6):411-418
OBJECTIVETo prepare the live recombinant vaccine of attenuated Salmonella typhimurium SL3261 expressing Helicobacter pylori (H. pylori) B subunit (UreB) and to determine whether it could be used as an oral vaccine against H. pylori infection.
METHODSUsing genomic DNA of H. pylori Sydney strain (SSI) as template, the H. pylori UreB gene fragment was amplified by PCR and subcloned into the expression vector pTC01. The recombinant plasmid pTC01-UreB was then transferred into LB5000 to obtain modified forms, and further conversed into the attenuated Salmonella typhimurium SL3261 to obtain recombinant SL3261/pCT01-UreB as an oral immunization reagent, which was then used to orally immunize Balb/c mice twice at a three-week interval. Twelve weeks later, anti-UreB IgA antibodies in intestinal fluid and IgG antibodies in sera were determined by ELISA. The relating data in control groups (including body weight, gastric inflammation, etc.) were also collected.
RESULTSThe sequencing analysis showed that the UreB gene fragment amplified by PCR was consistent with the sequence of the H. pylori UreB gene. The restriction enzyme digestion revealed that the correct pTC01-UreB was obtained. SDS-PAGE and Western blot showed that a 61KD protein was expressed in SL3261/pTC01-UreB, which could be recognized by anti-H. pylori UreB antiserum and was absent in the control containing only Salmonella typhimurium SL3261 strain. The multiple oral immunization with SL3261/pTC01-UreB could significantly induce H. pylori specific mucosal IgA response as well as serum IgG responses. IFN-gamma and IL-10 levels were significantly increased in SL3261/pTC01-UreB group, and no obvious side effect and change in gastric inflammation were observed.
CONCLUSIONThe attenuated vaccine of Salmonella typhimurium expressing H. pylori UreB can be used as an oral vaccine against H. pylori infection.
Animals ; Antibodies, Bacterial ; blood ; Bacterial Vaccines ; administration & dosage ; immunology ; Female ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Enzymologic ; Helicobacter Infections ; immunology ; prevention & control ; Helicobacter pylori ; enzymology ; genetics ; immunology ; Immunoglobulin G ; blood ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Mice ; Mice, Inbred BALB C ; Salmonella typhimurium ; genetics ; immunology ; metabolism ; Urease ; genetics ; immunology ; metabolism ; Vaccines, Attenuated ; genetics ; immunology ; Weight Loss
8.CD4+ and CD8+ T cells in gastric mucosa in children infected with Helicobacter pylori.
Zhong-yue LI ; Fei-bo CHEN ; Jie CHEN
Chinese Journal of Pediatrics 2005;43(6):453-456
OBJECTIVETo study the changes of gastric mucosal CD4(+) and CD8(+) T cells in Helicobacter pylori (Hp) infected children.
METHODSSeventy nine patients with digestive tract symptoms were assessed by endoscopy, rapid urease test and histology. Forty four patients had Hp positive chronic superficial gastritis (Hp(+)CSG) and 35 patients had Hp negative chronic superficial gastritis (Hp(-)CSG). Gastric biopsy specimens were obtained from each patient. Peripheral blood samples were obtained from 33 patients (12 with Hp(+)CSG, 21 with Hp(-)CSG). Hp infection was identified by rapid urease test and histology. Hp infection was confirmed when a patient was positive for both of these tests. Four pieces of gastric antrum mucosal specimens were placed in Hank's balanced salt solution containing 1 mmol/L dithiothreitol (DTT) and 1 mmol/L ethylenediamine tetraacetic acid (EDTA). The specimens were treated with collagenase type I (120 U/ml) for three hours at 37 degrees C with agitation. The mononuclear cells were collected by removing undigested material and washed three times with RPMI 1640. Isolated gastic mononuclear cells were stained with CD3-FITC (fluorescein isothiocyanate), CD4-PE (R-phycoerthrin), CD8-PerCP (Peridinin-chlorophyll-alpha-protein) and measured by flow cytometry. Mucosal T lymphocytes were gated for the expression of CD3. Peripheral blood lymphocyte subsets were analysed by direct immunofluorescence.
RESULTSThe percentage of isolated gastric mononuclear cells within the CD3 gate were 3.26 +/- 1.98 in Hp(-)CSG, 4.37 +/- 1.97 in Hp(+)CSG. Relative CD4(+)(%), CD8(+)(%) and CD4(+)/CD8(+) of the CD3(+) cells respectively were 23.74 +/- 10.37, 47.04 +/- 12.00, 0.52 +/- 0.23 in Hp(-)CSG group, 40.28 +/- 11.35, 27.91 +/- 8.84, 1.55 +/- 0.52 in Hp(+)CSG group. CD4(+)(%), CD4(+)/CD8(+) in Hp(+)CSG group were significantly higher than those of Hp(-)CSG group and CD8(+)(%) was lower than those of Hp(-)CSG group (P < 0.01). There were no significant differences in peripheral blood T lymphocyte subsets between the two groups.
CONCLUSIONThe difference of gastric T lymphocyte response between Hp(+)CSG and Hp(-)CSG in children indicated that the local cellular immune reaction may play a critical role in the pathogenesis of Hp infection.
Biopsy ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Child ; Female ; Fluorescent Antibody Technique, Direct ; Gastric Mucosa ; metabolism ; pathology ; Gastritis ; immunology ; microbiology ; pathology ; Gastroscopy ; Helicobacter Infections ; immunology ; microbiology ; pathology ; Helicobacter pylori ; immunology ; metabolism ; pathogenicity ; Humans ; Male ; Pyloric Antrum ; metabolism ; pathology ; Urease ; biosynthesis ; metabolism
9.Immunoprotective effects of Helicobacter pylori UreB and HpaA bivalence recombinant vaccine with inner adjuvant on experimental infection in mice.
Ya-fei MAO ; Jie YAN ; Yang XU
Journal of Zhejiang University. Medical sciences 2005;34(5):405-411
OBJECTIVETo determine the immunoprotective effects of rUreB and rHpaA bivalence genetic engineering vaccine with inner adjuvant of rLTB on BALB/c mice against H.pylori strain SS1 infection.
METHODSrUreB, rHpaA, rLTB-rUreB-rHpaA, rLTKA63, rLTB and rLTB were collected by NTA-Ni affinity chromatography. Western blot was applied to demonstrate the immunoreactivity of the recombinant protein antigens. Adjuvant activities of rLTB, rCTB and rLTB-rUreB-rHpaA were determined by GM1-ELISA. H.pylori strain SS1-infected BALB/c mouse modal was established to measure immunoprotective effects of different compositions of antigens and adjuvants. H.pylori in gastric biopsy specimens was examined by routine isolation method and silver staining method. Two ELISAs were established to detect specific S-IgA in gastric juices and specific IgA in sera of the immunized mice.
RESULTSrUreB, rHpaA and rLTB-rUreB-rHpaA were recognized by commercial antibody against whole cell of H.pylori and were able to combine to the bovine GM1. The protective rate in the mice immunized with single rUreB or rHpaA was lower than 70%. When using rUreB or rHpaA plus rLTB or rCTB, the positive rates increased to 75.0%-83.3%. With different combination of antigens and adjuvants, the immunoprotective rate of rLTB-jrUreB-rHpaA was as high as 100%, and then was 91.7% for rUreB+rHpaA+rCTB+rLTKA63 and was 90.9% for rUreB+rHpaA+rLTB. Both the rLTB and rCTB showed remarkable effects to induce specific IgA in sera and specific S-IgA in gastric juices of the immunized mice, and the former showed stronger S-IgA-inducing ability than the latter. The positive rates of specific IgA were basically identical to the corresponding mouse immunoprotective rates. S-IgA positive rates specific to rUreB and rHpaA in rLTB-rUreB-rHpaA immunized mice were 100% and 91.7%, respectively.
CONCLUSIONThe rUreB and rHpaA possess qualified immunoreactivity and antigenicity. The rLTB and rCTB can show adjuvant activity of mucosal immunization. The high immunoprotective rate of Helicobacter pylori UreB and HpaA bivalence recombinant vaccine with inner adjuvant in mice is associated with high dosage of rLTB, larger molecular weight of the antigen and the high levels of local specific S-IgA.
Adjuvants, Immunologic ; biosynthesis ; genetics ; Animals ; Bacterial Proteins ; biosynthesis ; genetics ; immunology ; Bacterial Vaccines ; immunology ; Carrier Proteins ; biosynthesis ; genetics ; immunology ; Female ; Genetic Engineering ; Helicobacter Infections ; prevention & control ; Helicobacter pylori ; immunology ; Immunoglobulin A ; blood ; metabolism ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; Vaccines, Synthetic ; immunology
10.Jak1/Stat3 Is an Upstream Signaling of NF-kappaB Activation in Helicobacter pylori-Induced IL-8 Production in Gastric Epithelial AGS Cells.
Boram CHA ; Joo Weon LIM ; Hyeyoung KIM
Yonsei Medical Journal 2015;56(3):862-866
Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-kappaB) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-kappaB and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and IkappaBalpha were assessed by Western blot analysis, and NF-kappaB activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-kappaB, determined by phosphorylation of IkappaBalpha and NF-kappaB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-kappaB and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-kappaB is inhibited and inflammatory cytokine expression is suppressed.
Blotting, Western
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DNA, Bacterial/analysis/genetics
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Epithelial Cells/metabolism
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Gastric Mucosa/drug effects/*immunology/microbiology
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Gene Expression Regulation/drug effects/*immunology
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Gene Expression Regulation, Bacterial
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Helicobacter Infections/immunology/*metabolism
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Helicobacter pylori/genetics/pathogenicity/*physiology
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Humans
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Interleukin-8/genetics/*metabolism
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Janus Kinase 1
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NF-kappa B/biosynthesis/*metabolism
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Phosphorylation
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RNA, Messenger/metabolism
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STAT3 Transcription Factor
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Signal Transduction/genetics