scholarly journals Production of ammonium by Helicobacter pylori mediates occludin processing and disruption of tight junctions in Caco-2 cells

Microbiology ◽  
2005 ◽  
Vol 151 (10) ◽  
pp. 3267-3276 ◽  
Author(s):  
Simon D. Lytton ◽  
Wolfgang Fischer ◽  
Wolfram Nagel ◽  
Rainer Haas ◽  
Franz X. Beck
Keyword(s):  
Molecular Weight ◽  
Helicobacter Pylori ◽  
Tight Junction ◽  
Tight Junctions ◽  
Ammonium Salts ◽  
Gastric Mucosal Damage ◽  
Soluble Form ◽  
Low Molecular Weight ◽  
Partial Recovery ◽  
H Pylori

Tight junctions, paracellular permeability barriers that define epithelial cell polarity, play an essential role in transepithelial transport, cell–cell adhesion and lymphocyte transmigration. They are also important for the maintenance of innate immune defence and intestinal antigen uptake. Ammonium () is elevated in the gastric aspirates of Helicobacter pylori-infected patients and has been implicated in the disruption of tight-junction functional integrity and the induction of gastric mucosal damage during H. pylori infection. The precise mechanism of the effect of ammonium and the molecular targets of ammonium in host tissue are not yet identified. To study the effects of ammonium on epithelial tight junctions, the human colon carcinoma cell line Caco-2 was cultured on permeable supports and the transepithelial resistance (TER) was measured at different time intervals following exposure to ammonium salts or H. pylori-derived ammonium. A biphasic response to treatment with ammonium was found. Acute exposure to ammonium salts or NH3/ derived from urea metabolism by wild-type H. pylori resulted in a 20–30 % decrease in TER. After 24 h, the NH4Cl-treated cells showed a partial recovery of TER. In contrast, the control culture, or cultures that were exposed to supernatants derived from urease-deficient H. pylori, showed no significant decrease in TER. Occludin-specific immunoblots revealed the expression of a low-molecular-weight form of occludin of 42 kDa upon NH3/ exposure. The results indicate that modulation of tight-junction function by H. pylori is ammonium-dependent and linked to the accumulation of a low-molecular-weight and detergent-soluble form of occludin.

scholarly journals Serum IgG antibodies against Helicobacter pylori low molecular weight antigens 50kDa, 30kDa and Urease A 26 kDa, along with vacuolating cytotoxin A are associated with the outcome of the infection

2020 ◽  
Vol 77 (4) ◽  
pp. 405-412
Author(s):  
Nebojsa Manojlovic ◽  
Ivana Tufegdzic ◽  
Elizabeta Ristanovic ◽  
Dubravko Bokonjic
Keyword(s):  
Gastric Cancer ◽  
Molecular Weight ◽  
Helicobacter Pylori ◽  
Functional Dyspepsia ◽  
Low Molecular Weight ◽  
Igg Antibodies ◽  
Vacuolating Cytotoxin ◽  
Specific Outcome ◽  
H Pylori ◽  
Topographic Distribution

Background/Aim. We designed and conducted this study due to the fact that results of the previous studies about seroreactivity to low-molecular-weight Helicobacter pylori antigens, cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA) in patients with gastric cancer and peptic ulcer were conflicting. Methods. The Western blot test was performed in 123 patients, 31 with gastric cancer, 31 with duodenal ulcer, 31 with gastric ulcer, 30 with gastritis and functional dyspepsia in order to determine IgG antibodies to H. pylori antigens (CagA, VacA, Heat shock protein 60kDa, Urease B 66 kDa, Flagellin 55kDa, 50kDa, 30 kDa, Urease A 26 kDa, 24 kDa). In this study we analyzed: seroreactivity to H. pylori antigens between group with functional dyspepsia and others; between grades of different histopathological parameters of inflammation of antral and corporal mucosa and between antrum-predominant gastritis and corpus-predominant gastritis + pangastritis groups. Results. It was shown that seropositivity to 50 kDa antigen could be used as a biomarker for functional dyspepsia, seropositivity to 30 kDa antigen for antrumpredominant gastritis and H. pylori colonization in the antrum, to UreaseA26 kDa antigen for pangastritis and corpus-predominant gastritis and degree of inflammation in the corpus. Seropositivity to VacA was the biomarker for gastric cancer and peptic ulcer taken together and inflammation of antral mucosa. Seropositivity to CagA was associated with more intensive inflammation of antral and corporal mucosa, Urease B66 kDa with inflammation of corpus mucosa, but neither of them with specific outcome of H. pylori infection and topographic distribution of gastric inflammation. Conclusion. Serum IgG antibodies to H. pylori antigens 50kDa, and VacA may represent useful biomarkers for the specific outcome of H. pylori infection, while serum antibodies to 30 kDa and UreaseA26 kDa antigens might be used as specific biomarkers for different topographic distribution of inflammation in gastric mucosa.

scholarly journals Role of Activated Protein C in Helicobacter pylori-Associated Gastritis

2000 ◽  
Vol 68 (5) ◽  
pp. 2863-2869 ◽  
Author(s):  
Satoko Oka ◽  
Esteban Cesar Gabazza ◽  
Yukiko Taguchi ◽  
Michihiko Yamaguchi ◽  
Shigehito Nakashima ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein C ◽  
Activated Protein C ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Gastric Corpus ◽  
H Pylori

ABSTRACT The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protect H. pylori-induced gastric mucosal damage.

scholarly journals Therapeutic effects of Zuojin Pill on Helicobacter pylori-induced chronic atrophic gastritis through JMJD2B/COX-2/VEGF signaling axis

2020 ◽  
Author(s):  
Shihua Wu ◽  
Chunmei Bao ◽  
Ruilin Wang ◽  
Xiaomei Zhang ◽  
Sijia Gao ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cell Viability ◽  
Atrophic Gastritis ◽  
Chronic Atrophic Gastritis ◽  
Gastric Mucosal Damage ◽  
Therapeutic Effects ◽  
Cox 2 ◽  
H Pylori

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

scholarly journals Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells

2019 ◽  
Vol 2 (11) ◽  
pp. 4777-4789 ◽  
Author(s):  
Bianca Menchicchi ◽  
Eleni Savvaidou ◽  
Christian Thöle ◽  
Andreas Hensel ◽  
Francisco M. Goycoolea
Keyword(s):  
Molecular Weight ◽  
Helicobacter Pylori ◽  
Dextran Sulfate ◽  
Low Molecular Weight ◽  
Gastric Cells

scholarly journals Helicobacter pylori-Induced Disruption of Monolayer Permeability and Proinflammatory Cytokine Secretion in Polarized Human Gastric Epithelial Cells

2013 ◽  
Vol 81 (3) ◽  
pp. 876-883 ◽  
Author(s):  
Maria Fiorentino ◽  
Hua Ding ◽  
Thomas G. Blanchard ◽  
Steven J. Czinn ◽  
Marcelo B. Sztein ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Tight Junction ◽  
Proinflammatory Cytokines ◽  
Barrier Function ◽  
Cytokine Secretion ◽  
Gastric Epithelial Cells ◽  
Content Type ◽  
Monolayer Permeability ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection of the stomach is related to the development of diverse gastric pathologies. The ability ofH. pylorito compromise epithelial junctional complexes and to induce proinflammatory cytokines is believed to contribute to pathogenesis. The purpose of this study was to use anin vitrohuman gastric epithelial model to investigate the ability ofH. pylorito affect permeability and the extent and polarity of the host inflammatory response. NCI-N87 monolayers were cocultured with live or heat-killedH. pylorior culture supernatants. Epithelial barrier function was measured by transepithelial electric resistance (TEER) analysis, diffusion of fluorescein isothiocyanate (FITC)-labeled markers, and immunostaining for tight junction proteins. Supernatants from both apical and basolateral chambers were tested for cytokine production by multiplex analysis.H. pyloricaused a significant decrease in TEER, an increased passage of markers through the infected monolayer, and severe disruption and mislocalization of ZO-1 and claudin-1 proteins. Cell viability was not altered byH. pylori, indicating that loss of barrier function could be attributed to a breakdown of tight junction integrity. Significantly high levels of cytokine secretion were induced by either viable or heat-killedH. pylori.H. pyloriaffects monolayer permeability of polarized human gastric epithelial cells. Proinflammatory cytokines were secreted in a polarized manner, mostly basolaterally. Live bacteria are required for disruption of tight junctions but not for the induction of cytokine secretion. The NCI-N87 cell line provides an excellent model for thein vitrostudy ofH. pyloripathogenesis and the epithelial cell host response to infection.

scholarly journals Digestion of the zinc in human milk, cow's milk and a commercial babyfood: some implications for human infant nutrition

1986 ◽  
Vol 55 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Peter Blakeborough ◽  
Michael I. Gurr ◽  
Dallyn N. Salter
Keyword(s):  
Molecular Weight ◽  
Human Milk ◽  
High Molecular Weight ◽  
Stomach Contents ◽  
Human Infant ◽  
Soluble Form ◽  
Cow’S Milk ◽  
Low Molecular Weight ◽  
Cow's Milk ◽  
Molecular Weight Form

1. The digestion of zinc present in human milk, cow's milk and a commercial babyfood was compared, using the piglet as a model for the human infant.2. In piglets given human milk the pH of stomach contents was approximately 1 and 0.4 units lower than that of animals given respectively cow's milk and babyfood. The pH values of intestinal contents were approximately neutral and did not vary with the type of feed.3. Hard casein curds were present throughout the stomachs and small intestines of animals fed on cow's milk or babyfood and between 55 and 70% Zn in these digesta samples were recovered in an insoluble form by centrifugation. In contrast, little solid material was observed in the digesta of animals fed on human milk, and 57 and 93% respectively of the Zn in digesta were recovered in a soluble form in the stomach and small intestine.4. Soluble fractions prepared by centrifugation of digesta were analysed by filtration on Sephadex G-150. After any of the three feeds, soluble Zn in stomach contents was mainly in a low-molecular-weight form. In intestinal samples, however, Zn was present in low- and high-molecular-weight forms. Whilst there were similar amounts of Zn in the low-molecular-weight form in all samples, approximately three times as much of the total intestinal Zn was in a soluble high-molecular-weight form complexed to proteins in the animals fed on human milk compared with those fed on cow's milk or babyfood.5. Analysis of protein-bound soluble Zn in intestinal samples on SDS-polyacrylamide gels resulted in a similar pattern of proteins for all feeds. Results indicated that at least some of these proteins were derived from intestinal secretions of the piglet.6. Some implications of these results in respect of the mode of digestion of Zn and its biological availability to the human infant are discussed.

scholarly journals Follow-up analysis and histopathological study of gastric mucosa in patients with Helicobacter pylori infection

2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110553
Author(s):  
Guang Zhao ◽  
Zhishang Zhang ◽  
Baohui Li ◽  
Silin Huang ◽  
Wensi Li ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Intraepithelial Neoplasia ◽  
Mucosal Damage ◽  
Helicobacter Pylori Infection ◽  
Gastric Mucosal Damage ◽  
Histopathological Study ◽  
Significant Difference ◽  
H Pylori

Objective To investigate the histomorphological characteristics of the gastric mucosa and the prognosis in patients with Helicobacter pylori infection. Methods Progressive damage to the gastric mucosa was examined by immunohistochemistry in 2294 patients with H. pylori infection and follow-up information was analyzed. Results H. pylori initially colonized the mucus layer covered by the gastric mucosa epithelium, then selectively adhered to and destroyed the surface mucus cells causing intra-gastric and extra-gastric lesions. Gastric mucosal damage induced by H. pylori was divided into five stages according to the depth of H. pylori invasion and degree of lesion deterioration: mucilaginous, surface mucocellular, lamina propria lesion, mucosal atrophy, and intraepithelial neoplasia stages. Morphological follow-up analysis revealed no significant difference in 6-month curative effects between stage I and stage II, but significant differences were found between stages II and III, stages III and IV, and between stages IV and stage V, respectively. Conclusions This novel staging strategy may be a valuable tool for diagnosing and predicting the results of gastric mucosal damage induced by H. pylori infection.

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