scholarly journals Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells

2007 ◽  
Vol 75 (8) ◽  
pp. 4030-4039 ◽  
Author(s):  
Song-Ze Ding ◽  
Yutaka Minohara ◽  
Xue Jun Fan ◽  
Jide Wang ◽  
Victor E. Reyes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Dna Fragmentation ◽  
Inflammatory Cytokines ◽  
Ros Generation ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori infection is associated with altered gastric epithelial cell turnover. To evaluate the role of oxidative stress in cell death, gastric epithelial cells were exposed to various strains of H. pylori, inflammatory cytokines, and hydrogen peroxide in the absence or presence of antioxidant agents. Increased intracellular reactive oxygen species (ROS) were detected using a redox-sensitive fluorescent dye, a cytochrome c reduction assay, and measurements of glutathione. Apoptosis was evaluated by detecting DNA fragmentation and caspase activation. Infection with H. pylori or exposure of epithelial cells to hydrogen peroxide resulted in apoptosis and a dose-dependent increase in ROS generation that was enhanced by pretreatment with inflammatory cytokines. Basal levels of ROS were greater in epithelial cells isolated from gastric mucosal biopsy specimens from H. pylori-infected subjects than in cells from uninfected individuals. H. pylori strains bearing the cag pathogenicity island (PAI) induced higher levels of intracellular oxygen metabolites than isogenic cag PAI-deficient mutants. H. pylori infection and hydrogen peroxide exposure resulted in similar patterns of caspase 3 and 8 activation. Antioxidants inhibited both ROS generation and DNA fragmentation by H. pylori. These results indicate that bacterial factors and the host inflammatory response confer oxidative stress to the gastric epithelium during H. pylori infection that may lead to apoptosis.

scholarly journals Helicobacter pylori Induces Gastric Epithelial Cell Apoptosis in Association with Increased Fas Receptor Expression

1999 ◽  
Vol 67 (8) ◽  
pp. 4237-4242 ◽  
Author(s):  
Nicola L. Jones ◽  
Andrew S. Day ◽  
Hilary A. Jennings ◽  
Philip M. Sherman
Keyword(s):  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Receptor Expression ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Fas Receptor ◽  
Epithelial Cell Apoptosis ◽  
H Pylori

ABSTRACT The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection withHelicobacter pylori in vivo are unknown. To determine whether H. pylori directly induces apoptosis of gastric epithelial cells in vitro and to define the role of the Fas-Fas ligand signal transduction cascade, human gastric epithelial cells were infected with H. pylori for up to 72 h under microaerophilic conditions. As assessed by both transmission electron microscopy and fluorescence microscopy, incubation with acagA-positive, cagE-positive, VacA-positive clinical H. pylori isolate stimulated an increase in apoptosis compared to the apoptosis of untreated AGS cells (16.0% ± 2.8% versus 5.9% ± 1.4%, P < 0.05) after 72 h. In contrast, apoptosis was not detected following infection withcagA-negative, cagE-negative, VacA-negative clinical isolates or a Campylobacter jejuni strain. In addition to stimulating apoptosis, infection with H. pylorienhanced Fas receptor expression in AGS cells to a degree comparable to that of treatment with a positive control, gamma interferon (12.5 ng/ml) (148% ± 24% and 167% ± 24% of control, respectively). The enhanced Fas receptor expression was associated with increased sensitivity to Fas-mediated cell death. Ligation of the Fas receptor with an agonistic monoclonal antibody resulted in an increase in apoptosis compared to the apoptosis of cells infected with the bacterium alone (38.5% ± 7.1% versus 16.0% ± 2.8%,P < 0.05). Incubation with neutralizing anti-Fas antibody did not prevent apoptosis of H. pylori-infected cells. Taken together, these findings demonstrate that the gastric pathogen H. pylori stimulates apoptosis of gastric epithelial cells in vitro in association with the enhanced expression of the Fas receptor. These data indicate a role for Fas-mediated signaling in the programmed cell death that occurs in response toH. pylori infection.

scholarly journals α-Lipoic Acid Inhibits IL-8 Expression by Activating Nrf2 Signaling in Helicobacter pylori-infected Gastric Epithelial Cells

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2524 ◽  
Author(s):  
Seoyeon Kyung ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Lipoic Acid ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Gastric Epithelial Cells ◽  
Gastric Diseases ◽  
Ags Cells ◽  
H Pylori

Helicobacter pylori (H. pylori) causes gastritis and gastric cancers. Oxidative stress is involved in the pathological mechanism of H. pylori-induced gastritis and gastric cancer induction. Therefore, reducing oxidative stress may be beneficial for preventing the development of H. pylori-associated gastric diseases. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator for the expression of antioxidant enzyme heme oxygenase-1 (HO-1), which protects cells from oxidative injury. α-Lipoic acid (α-LA), a naturally occurring dithiol, shows antioxidant and anti-inflammatory effects in various cells. In the present study, we examined the mechanism by which α-LA activates the Nrf2/HO-1 pathway, suppresses the production of pro-inflammatory cytokine interleukine-8 (IL-8), and reduces reactive oxygen species (ROS) in H. pylori-infected AGS cells. α-LA increased the level of phosphorylated and nuclear-translocated Nrf2 by decreasing the amount of Nrf2 sequestered in the cytoplasm by complex formation with Kelch-like ECH1-associated protein 1 (KEAP 1). By using exogenous inhibitors targeting Nrf2 and HO-1, we showed that up-regulation of activated Nrf2 and of HO-1 results in the α-LA-induced suppression of interleukin 8 (IL-8) and ROS. Consumption of α-LA-rich foods may prevent the development of H. pylori-associated gastric diseases by decreasing ROS-mediated IL-8 expression in gastric epithelial cells.

scholarly journals Inhibitory Effect of Astaxanthin on Helicobacter pylori- Induced Matrixmetalloproteinase Expression in Gastric Epithelial AGS Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1132-1132
Author(s):  
Jimin Lee ◽  
Suji Bae ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Cell Invasion ◽  
Pcr Analysis ◽  
Epithelial Cell Line ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Extracellular Matrix Components ◽  
H Pylori

Abstract Objectives Matrix metalloproteinases (MMPs), enzymes capable of degrading extracellular matrix components (ECM), are believed to be associated with carcinogenesis. Helicobacter pylori (H. pylori) infection increased oxidative stress and promotes the invasion and metastasis of gastric cells by inducing expression of MMPs. Reactive oxygen species (ROS) mediates expression of MMPs. Astaxanthin, a xanthophyll carotenoid, has strong antioxidant and anticancer properties. The present study was aimed to investigate whether astaxanthin inhibits H. pylori-induced MMPs expression in human gastric epithelial cells by redicing oxidative stress. Methods AGS cells, human gastric epithelial cell line, were pre-treated with astaxanthin for 3 hours prior to H. pylori (cag A positive NCTC 11,637 strains) infection. The cells treated with or without astaxanthin were cultured for 24 hours in the presence of H. pylori. mRNA expression of MMP-7 and MMP-10 was measured by real time PCR analysis. ROS levels were determined using dichlorofluorescin fluorescence. Protein levels of MMPs were determined using western blot analysis. Invasion assay was performed for the cells in the upper and lower compartments in Matrigel-coated filters and the cells were examined under a laser scanning confocal microscope. Results H. pylori increased ROS levels and expression of MMP-7 and MMP-10 in AGS cells. H. pylori induced cell invasion. Astaxanthin suppressed the expression of H. pylori-induced MMP-7 and MMP-10 at the mRNA and protein level. Conclusions H. pylori infection induces expression of MMP-7 and MMP-10 and cell invasion, which may be mediated with increased ROS in gastric epithelial cells. Astaxanthin inhibits MMP expression by reducingROS levels in H. pylori-infected gastric epithelial cells. Funding Sources This study was supported by a Brain Korea 21 FOUR Project, Yonsei University, Seoul, Republic of Korea.

scholarly journals Helicobacter pylori VacA Induces Programmed Necrosis in Gastric Epithelial Cells

2011 ◽  
Vol 79 (7) ◽  
pp. 2535-2543 ◽  
Author(s):  
Jana N. Radin ◽  
Christian González-Rivera ◽  
Susan E. Ivie ◽  
Mark S. McClain ◽  
Timothy L. Cover
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Human Stomach ◽  
Gastric Epithelial Cells ◽  
Wild Type ◽  
Programmed Necrosis ◽  
Content Type ◽  
H Pylori

ABSTRACTHelicobacter pyloriis a Gram-negative bacterium that colonizes the human stomach and contributes to the development of peptic ulcer disease and gastric cancer. The secreted pore-forming toxin VacA is one of the major virulence factors ofH. pylori. In the current study, we show that AZ-521 human gastric epithelial cells are highly susceptible to VacA-induced cell death. Wild-type VacA causes death of these cells, whereas mutant VacA proteins defective in membrane channel formation do not. Incubation of AZ-521 cells with wild-type VacA results in cell swelling, poly(ADP-ribose) polymerase (PARP) activation, decreased intracellular ATP concentration, and lactate dehydrogenase (LDH) release. VacA-induced death of these cells is a caspase-independent process that results in cellular release of histone-binding protein high mobility group box 1 (HMGB1), a proinflammatory protein. These features are consistent with the occurrence of cell death through a programmed necrosis pathway and suggest that VacA can be included among the growing number of bacterial pore-forming toxins that induce cell death through programmed necrosis. We propose that VacA augmentsH. pylori-induced mucosal inflammation in the human stomach by causing programmed necrosis of gastric epithelial cells and subsequent release of proinflammatory proteins and may thereby contribute to the pathogenesis of gastric cancer and peptic ulceration.

scholarly journals Pre-Treatment with Grape Seed Extract Reduces Inflammatory Response and Oxidative Stress Induced by Helicobacter pylori Infection in Human Gastric Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 943
Author(s):  
Jose Manuel Silvan ◽  
Alba Gutierrez-Docio ◽  
Esperanza Guerrero-Hurtado ◽  
Lucia Domingo-Serrano ◽  
Ana Blanco-Suarez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Seed Extract ◽  
Gastric Epithelial Cells ◽  
Pre Treatment ◽  
H Pylori ◽  
And Oxidative Stress

Helicobacter pylori (H. pylori) is a pathogenic bacteria identified as a potential risk factor for gastritis, gastric ulcers and gastric cancer. During the stomach colonization, H. pylori triggers a strong inflammatory response and subsequent oxidative stress, which are associated with tissue damage. For this reason, it is of particular interest to develop alternative natural tools that enable modulation of the associated damaging immune response. With this purpose, we obtained grape seed extract (GSE) from sweet (not fermented) food grade seeds. The aim of our study was to investigate the effect of GSE and its two enriched procyanidins fractions (OPC and PPC) on the inflammatory process and oxidative stress produced by different H. pylori strains in human gastric epithelial cells (AGS). Anti-inflammatory activity was evaluated by measuring the level of interleukin-8 (IL-8) secretion. IL-8 production was significantly reduced in H. pylori-infected human gastric epithelial cells pre-treated with GSE or its enriched fractions when compared with non-pre-treated infected cells (from 21.6% to 87.8%). Pre-treatment with GSE or its fractions significantly decreased intracellular reactive oxygen species (ROS) production in AGS cells after infection, depending on the H. pylori strain. Our results also showed that GSE and its fractions demonstrate antibacterial activity against all strains of H. pylori used in the study. This work demonstrates the effectiveness of GSE enriched in procyanidins against the main events associated with H. pylori infection.

scholarly journals Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1320 ◽  
Author(s):  
Suhn Kim ◽  
Joo Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Mitochondrial Dysfunction ◽  
Peroxisome Proliferator ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Ppar Γ ◽  
H Pylori

Helicobacter pylori (H. pylori) infection leads to gastric inflammation, peptic ulcer and gastric carcinoma. H. pylori activates NADPH oxidase and increases reactive oxygen species (ROS), which induce NF-κB activation and IL-8 expression in gastric epithelial cells. Dysfunctional mitochondria trigger inflammatory cytokine production. Peroxisome proliferator-activated receptors-γ (PPAR-γ) regulate inflammatory response. Astaxanthin is a powerful antioxidant that protects cells against oxidative stress. The present study was aimed at determining whether astaxanthin inhibits H. pylori-induced mitochondrial dysfunction, NF-κB activation, and IL-8 expression via PPAR-γ activation in gastric epithelial cells. Gastric epithelial AGS cells were treated with astaxanthin, NADPH oxidase inhibitor apocynin and PPAR-γ antagonist GW9662, and infected with H. pylori. As a result, H. pylori caused an increase in intracellular and mitochondrial ROS, NF-κB activation and IL-8 expression, but decreased mitochondrial membrane potential and ATP level. Astaxanthin inhibited H. pylori-induced alterations (increased ROS, mitochondrial dysfunction, NF-κB activation, and IL-8 expression). Astaxanthin activated PPAR-γ and its target gene catalase in H. pylori-infected cells. Apocynin reduced ROS and inhibited IL-8 expression while astaxanthin did not affect NADPH oxidase activity. Inhibitory effects of astaxanthin on ROS levels and IL-8 expression were suppressed by addition of GW9662. In conclusion, astaxanthin inhibits H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8 expression by activating PPAR-γ and catalase in gastric epithelial cells. Astaxanthin may be beneficial for preventing oxidative stress-mediated gastric inflammation-associated H. pylori infection.

scholarly journals Effects ofHelicobacter pyloriand Heat Shock Protein 70 on the Proliferation of Human Gastric Epithelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Liping Tao ◽  
Hai Zou ◽  
Zhimin Huang
Keyword(s):  
Helicobacter Pylori ◽  
Heat Shock ◽  
Epithelial Cells ◽  
Heat Shock Protein ◽  
Mtt Assay ◽  
Heat Shock Protein 70 ◽  
Hsp70 Expression ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
H Pylori

Infection ofHelicobacter pylori (H. pylori)changed the proliferation of gastric epithelial cells and decreased the expression of heat shock protein 70 (HSP70). However, the effects ofH. pylorion the proliferation of gastric epithelial cells and the roles of HSP70 during the progress need further investigation.Objective.To investigate the effects ofHelicobacter pylori (H. pylori)and heat shock protein 70 (HSP70) on the proliferation of human gastric epithelial cells.Methods. H. pyloriand a human gastric epithelial cell line (AGS) were cocultured. The proliferation of AGS cells was quantitated by an MTT assay, and the expression of HSP70 in AGS cells was detected by Western blotting. HSP70 expression in AGS cells was silenced by small interfering RNA (siRNA) to investigate the role of HSP70. ThesiRNA-treated AGS cells were cocultured withH. pyloriand cell proliferation was measured by an MTT assay.Results.The proliferation of AGS cells was accelerated by coculturing withH. pylorifor 4 and 8 h, but was suppressed at 24 and 48 h. HSP70 expression was decreased in AGS cells infected byH. pylorifor 48 h. The proliferation in HSP70-silenced AGS cells was inhibited after coculturing withH. pylorifor 24 and 48 h compared with the control group.Conclusions.Coculture ofH. pylorialtered the proliferation of gastric epithelial cells and decreased HSP70 expression. HSP70 knockdown supplemented the inhibitory effect ofH. pylorion proliferation of epithelial cells. These results indicate that the effects ofH. pylorion the proliferation of gastric epithelial cells at least partially depend on the decreased expression of HSP70 induced by the bacterium.

scholarly journals TIFA Signaling in Gastric Epithelial Cells Initiates the cag Type 4 Secretion System-Dependent Innate Immune Response to Helicobacter pylori Infection

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Alevtina Gall ◽  
Ryan G. Gaudet ◽  
Scott D. Gray-Owen ◽  
Nina R. Salama
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Secretion System ◽  
Innate Immune ◽  
Gastric Ulcers ◽  
Bacterial Clearance ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence. Cytosolic delivery of proinflammatory bacterial factors through the cag type 4 secretion system ( cag -T4SS) has long been appreciated as the major mechanism by which gastric epithelial cells detect H. pylori . Classically attributed to the peptidoglycan sensor NOD1, recent work has highlighted the role of NOD1-independent pathways in detecting H. pylori ; however, the bacterial and host factors involved have remained unknown. Here, we show that bacterially derived heptose-1,7-bisphosphate (HBP), a metabolic precursor in lipopolysaccharide (LPS) biosynthesis, is delivered to the host cytosol through the cag -T4SS, where it activates the host tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA)-dependent cytosolic surveillance pathway. This response, which is independent of NOD1, drives robust NF-κB-dependent inflammation within hours of infection and precedes NOD1 activation. We also found that the CagA toxin contributes to the NF-κB-driven response subsequent to TIFA and NOD1 activation. Taken together, our results indicate that the sequential activation of TIFA, NOD1, and CagA delivery drives the initial inflammatory response in gastric epithelial cells, orchestrating the subsequent recruitment of immune cells and leading to chronic gastritis. IMPORTANCE H. pylori is a globally prevalent cause of gastric and duodenal ulcers and cancer. H. pylori antibiotic resistance is rapidly increasing, and a vaccine remains elusive. The earliest immune response to H. pylori is initiated by gastric epithelial cells and sets the stage for the subsequent immunopathogenesis. This study revealed that host TIFA and H. pylori -derived HBP are critical effectors of innate immune signaling that account for much of the inflammatory response to H. pylori in gastric epithelial cells. HBP is delivered to the host cell via the cag -T4SS at a time point that precedes activation of the previously described NOD1 and CagA inflammatory pathways. Manipulation of the TIFA-driven immune response in the host and/or targeting of ADP-heptose biosynthesis enzymes in H. pylori may therefore provide novel strategies that may be therapeutically harnessed to achieve bacterial clearance.

Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro

2018 ◽  
Vol 9 (5) ◽  
pp. 829-841 ◽  
Author(s):  
V. Garcia-Castillo ◽  
H. Zelaya ◽  
A. Ilabaca ◽  
M. Espinoza-Monje ◽  
R. Komatsu ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Morphological Changes ◽  
Helicobacter Pylori Infection ◽  
Lactobacillus Fermentum ◽  
Gastric Tissue ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
H Pylori

Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans.

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