Cell damage and proliferation in human gastric mucosa infected by Helicobacter pylori?A comparison before and after H pylori eradication in non-atrophic gastritis

ABSTRACT Helicobacter pylori colonizes the human gastric mucosa, causing inflammation that leads to atrophic gastritis, and it can cause peptic ulcer and gastric cancer. We show that polyphenol administration to mice experimentally infected by H. pylori or treated with VacA toxin can limit gastric epithelium damage, an effect that may be linked to VacA inhibition.

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Oxidative-stress-related proteome changes in Helicobacter pylori-infected human gastric mucosa

Biochemical Journal ◽

10.1042/bj20031208 ◽

2004 ◽

Vol 379 (2) ◽

pp. 291-299 ◽

Cited By ~ 38

Author(s):

Hye Yeon BAEK ◽

Joo Weon LIM ◽

Hyeyoung KIM ◽

Jung Mogg KIM ◽

Joo Sung KIM ◽

...

Keyword(s):

Oxidative Stress ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Cell Damage ◽

Blue Staining ◽

Human Gastric Mucosa ◽

Heat Shock Protein 60 ◽

Gastric Diseases ◽

Tryptic Fragment ◽

H Pylori

Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa from the patients with erosive gastritis, peptic ulcer or gastric cancer, which were either infected or not with H. pylori, was used to determine the differentially expressed proteins by H. pylori in the human gastric mucosa in order to investigate the pathogenic mechanism of H. pylori-induced gastric diseases. Prior to the experiment, the expression of the main 18 proteins were identified in the gastric mucosa and used for a proteome map of the human gastric mucosa. Using two-dimensional electrophoresis of the protein isolated from the H. pylori-infected tissues, Coomassie Brilliant Blue staining and computerized analysis of the stained gel, the expression of eight proteins were altered in the H. pylori-infected tissues compared with the non-infected tissues. MS analysis (matrix-assisted laser desorption/ionization–time of flight MS) of the tryptic fragment and a data search allowed the the identification of the four increased proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor, aldehyde dehydrogenase 2 and l-lactate dehydrogenase B chain) and the four decreased proteins (intracellular chloride channel protein 1, glutathione S-transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori infection in the gastric mucosa. These proteins are related to cell proliferation, carcinogenesis, cytoskeletal function and cellular defence mechanism. The common feature is that these proteins are related to oxidative-stress-mediated cell damage. In conclusion, the established gastric mucosal proteome map might be useful for detecting the disease-related protein changes. The H. pylori-induced alterations in protein expression demonstrate the involvement of oxidative stress in the pathogenesis of H. pylori-induced gastric diseases, including inflammation, ulceration and carcinogenesis.

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Helicobacter pylori (H. pylori) infection increases IL-8 and IL-6 production from human gastric mucosa

Gastroenterology ◽

10.1016/0016-5085(95)27387-5 ◽

1995 ◽

Vol 108 (4) ◽

pp. A769

Author(s):

T. Ando ◽

K. Kusugami ◽

M. Sakakibara ◽

T. Shimizu ◽

M. Shinoda ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Human Gastric Mucosa ◽

H Pylori

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Helicobacter pylori–binding nonacid glycosphingolipids in the human stomach

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.004854 ◽

2018 ◽

Vol 293 (44) ◽

pp. 17248-17266 ◽

Cited By ~ 6

Author(s):

Chunsheng Jin ◽

Angela Barone ◽

Thomas Borén ◽

Susann Teneberg

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Structural Complexity ◽

Human Stomach ◽

Carbohydrate Binding ◽

Human Gastric Mucosa ◽

H Pylori ◽

Contrast Information

Helicobacter pylori has a number of well-characterized carbohydrate-binding adhesins (BabA, SabA, and LabA) that promote adhesion to the gastric mucosa. In contrast, information on the glycoconjugates present in the human stomach remains unavailable. Here, we used MS and binding of carbohydrate-recognizing ligands to characterize the glycosphingolipids of three human stomachs from individuals with different blood group phenotypes (O(Rh−)P, A(Rh+)P, and A(Rh+)p), focusing on compounds recognized by H. pylori. We observed a high degree of structural complexity, and the composition of glycosphingolipids differed among individuals with different blood groups. The type 2 chain was the dominating core chain of the complex glycosphingolipids in the human stomach, in contrast to the complex glycosphingolipids in the human small intestine, which have mainly a type 1 core. H. pylori did not bind to the O(Rh−)P stomach glycosphingolipids, whose major complex glycosphingolipids were neolactotetraosylceramide, the Lex, Lea, and H type 2 pentaosylceramides, and the Ley hexaosylceramide. Several H. pylori-binding compounds were present among the A(Rh+)P and A(Rh+)p stomach glycosphingolipids. Ligands for BabA-mediated binding of H. pylori were the Leb hexaosylceramide, the H type 1 pentaosylceramide, and the A type 1/ALeb heptaosylceramide. Additional H. pylori-binding glycosphingolipids recognized by BabA-deficient strains were lactosylceramide, lactotetraosylceramide, the x2 pentaosylceramide, and neolactohexaosylceramide. Our characterization of human gastric receptors required for H. pylori adhesion provides a basis for the development of specific compounds that inhibit the binding of this bacterium to the human gastric mucosa.

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Chronic gastritis and Helicobacter pylori in digestive form of Chagas' disease

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651993000200002 ◽

1993 ◽

Vol 35 (2) ◽

pp. 117-121 ◽

Cited By ~ 9

Author(s):

A. J. A. Barbosa ◽

D. M. M. Queiroz ◽

A. M. M. F. Nogueira ◽

M. J. A. Roquette Reis ◽

E. N. Mendes ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Atrophic Gastritis ◽

Chagas Disease ◽

Chronic Gastritis ◽

Antral Mucosa ◽

Common Cause ◽

Superficial Gastritis ◽

H Pylori ◽

Inflammatory Changes

Patients with the digestive form of Chagas'disease frequently present chronic gastritis. As the microorganism Helicobacter pylori is now accepted as the most common cause of human chronic gastritis, the present work was undertaken to verify a possible relationship between the presence of this bacterium and inflammatory changes of antral mucosa in chagasic patients. Seventeen chagasics, with megaesophagus and or megacolon were studied. Fragments from two different regions of antral mucosa were obtained by endoscopy, fixed in 4% neutral formaldehyde and embedded in paraffin. The sections were stained by haematoxylin and eosin for histology analysis, and by carbolfuchsin for H. pylori identification. H. pylori was found in 16 (94.1%) chagasic patients, all of them presenting chronic gastritis. Superficial gastritis was seen in 9 (52.9%) while atrophic gastritis was present in 8 (47.1%) patients. H. pylori was present on gastric mucosa of 8 (100%) patients with atrophic gastritis and of 8 (88.8%) patients with superficial gastritis. We concluded that the microorganism H. pylori should be considered a possible factor connected with the etiopathogenesis of chronic superficial and atrophic gastritis frequently observed in patients with the digestive form of Chagas' disease.

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Helicobacter pylori Distribution in Human Gastric Mucosa with Chronic, Atrophic Gastritis

Digestive Endoscopy ◽

10.1111/j.1443-1661.1992.tb00102.x ◽

1992 ◽

Vol 4 (4) ◽

pp. 376-381 ◽

Cited By ~ 3

Author(s):

Yoshihiro KOHLI ◽

Takuji KATO ◽

Shigeji ITO ◽

Makoto IWAI ◽

Masanori HATA ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Human Gastric Mucosa

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Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.

Journal of Experimental Medicine ◽

10.1084/jem.179.5.1653 ◽

1994 ◽

Vol 179 (5) ◽

pp. 1653-1658 ◽

Cited By ~ 383

Author(s):

J L Telford ◽

P Ghiara ◽

M Dell'Orco ◽

M Comanducci ◽

D Burroni ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

Gastric Mucosa ◽

Chronic Infection ◽

Gastric Disease ◽

Human Gastric Mucosa ◽

Gastric Lesions ◽

Gram Negative ◽

H Pylori ◽

Cytotoxin Gene

The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.

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Downregulation of Interleukin- (IL-) 17 through Enhanced Indoleamine 2,3-Dioxygenase (IDO) Induction by Curcumin: A Potential Mechanism of Tolerance towards Helicobacter pylori

Journal of Immunology Research ◽

10.1155/2018/3739593 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Tiziana Larussa ◽

Serena Gervasi ◽

Rita Liparoti ◽

Evelina Suraci ◽

Raffaella Marasco ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Antimicrobial Properties ◽

Human Gastric Mucosa ◽

T Cell Apoptosis ◽

Indoleamine 2,3 Dioxygenase ◽

Treated Sample ◽

Tryptophan Catabolism ◽

Gastric Biopsies ◽

H Pylori

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-Helicobacter pylori (H. pylori) agent, but mechanisms underlying its helpful activity are still not clear. Indoleamine 2,3-dioxygenase (IDO) promotes the effector T cell apoptosis by catalyzing the rate-limiting first step in tryptophan catabolism, and its high expression in H. pylori-infected human gastric mucosa attenuates Th1 and Th17 immune response. The aim of this study was to investigate the role of curcumin in modulating the expression of IL-17 and IDO in H. pylori-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 μM curcumin. In H. pylori-infected patients (n=21), IL-17 was significantly lower, both in gastric biopsies (p=0.0003) and culture supernatant (p=0.0001) while IDO significantly increased (p<0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of H. pylori-infected patients (n=15), samples treated with curcumin in addition to IDO inhibitor 1-methyl-L-tryptophan (1-MT) showed a higher expression of IL-17 compared with untreated samples and curcumin-treated alone (p<0.00001). Curcumin downregulates IL-17 production through the induction of IDO in H. pylori-infected human gastric mucosa, suggesting its role in dampening H. pylori-induced immune-mediated inflammatory changes.

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Interleukin-12 Drives the Th1 Signaling Pathway in Helicobacter pylori-Infected Human Gastric Mucosa

Infection and Immunity ◽

10.1128/iai.01446-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 1738-1744 ◽

Cited By ~ 34

Author(s):

Antonia Pellicanò ◽

Ladislava Sebkova ◽

Giovanni Monteleone ◽

Giovanni Guarnieri ◽

Maria Imeneo ◽

...

Keyword(s):

Helicobacter Pylori ◽

Transcription Factors ◽

Gastric Mucosa ◽

Enzyme Linked Immunosorbent Assay ◽

Human Gastric Mucosa ◽

Organ Cultures ◽

Gastric Biopsies ◽

Ifn Γ ◽

H Pylori ◽

Cell Commitment

ABSTRACT In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1) commitment in Helicobacter pylori-infected human gastric mucosa. The levels of gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-12 in total extracts of gastric biopsies taken from H. pylori-infected and uninfected patients were determined by an enzyme-linked immunosorbent assay. The levels of signal transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed in T cells (T-bet) in total proteins extracted from gastric biopsies were determined by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on expression of Th1 transcription factors and the levels of IFN-γ in organ cultures of H. pylori-infected biopsies was examined. Increased levels of IFN-γ and IL-12 were found in gastric biopsy samples of H. pylori-infected patients compared to the levels in uninfected patients. In addition, H. pylori-infected biopsies exhibited high levels of expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-γ and expression of Th1 transcription factors were associated with greater infiltration of mononuclear cells in the gastric mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6 were not associated with the intensity of mononuclear cell infiltration. In ex vivo organ cultures of H. pylori-infected biopsies, neutralization of endogenous IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced IFN-γ production. Our data indicated that IL-12 contributes to the Th1 cell commitment in H. pylori-infected human gastric mucosa.

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Tissue transglutaminase activity in human gastric mucosa according to Helicobacter pylori infection

Experimental Biology and Medicine ◽

10.1177/1535370218819423 ◽

2018 ◽

Vol 243 (15-16) ◽

pp. 1161-1164

Author(s):

Maria Pina Dore ◽

Giovanni Mario Pes ◽

Alessandra Errigo ◽

Alessandra Manca ◽

Giuseppe Realdi

Keyword(s):

Helicobacter Pylori ◽

Animal Models ◽

Gastric Mucosa ◽

Natural History ◽

Tissue Transglutaminase ◽

Helicobacter Pylori Infection ◽

Human Gastric Mucosa ◽

Antral Mucosa ◽

History Of ◽

H Pylori

Tissue transglutaminase (t-TG) is a multifunctional protein involved in the healing of gastric erosions and ulcers in animal models. The aim of this study was to measure gastric t-TG activity in patients with dyspepsia according to Helicobacter pylori infection and cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) subtype status. Patients undergoing upper endoscopy not taking any medications were enrolled. Tissue-TG activity was determined in homogenates of antral specimens using a radiometric assay and was expressed in pmol/mg. The cagA and vacA genotypes were determined by PCR amplification using gene-specific oligoprimers. Data from 46 patients were available (17 of them were positive for H. pylori). Antral t-TG activity was significantly increased in H. pylori positive patients compared to H. pylori negative patients (6437 ± 3691 vs. 3773 ± 1530 pmol/mg; P = 0.001) according to Mann–Whitney U test. Patients with H. pylori negative gastritis had higher t-TG activity than patients with normal gastric mucosa. The specimens infected with cagA positive strains (72%) displayed greater t-TG activity than cagA negative samples (7358 ± 4318 vs. 4895 ± 1062 pmol/mg; P = 0.237). Similarly, t-TG activity was higher in H. pylori vacA s1/m1 strains vs. vacA s1/m2 (7429 vs. 5045 pmol/mg; P = 0.744), and vacA s1/m1 vs. s2/m2 (7429 vs. 4489 pmol/mg; P = 0.651) but the results were not significant. No differences were found between histology, endoscopy features and t-TG activity. These results show that t-TG activity is significantly greater in gastritis associated with H. pylori infection, suggesting that this enzyme is induced by inflammation and may have an important role in the natural history of human gastritis. Impact statement Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.

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