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.

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.

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 Inhibitory Effect of β-Carotene on Helicobacter pylori-Induced TRAF Expression and Hyper-Proliferation in Gastric Epithelial Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 637 ◽  
Author(s):  
Yongchae Park ◽  
Hanbit Lee ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Gastric Epithelial Cells ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
H Pylori ◽  
Β Carotene

Helicobacter pylori infection causes the hyper-proliferation of gastric epithelial cells that leads to the development of gastric cancer. Overexpression of tumor necrosis factor receptor associated factor (TRAF) is shown in gastric cancer cells. The dietary antioxidant β-carotene has been shown to counter hyper-proliferation in H. pylori-infected gastric epithelial cells. The present study was carried out to examine the β-carotene mechanism of action. We first showed that H. pylori infection decreases cellular IκBα levels while increasing cell viability, NADPH oxidase activity, reactive oxygen species production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, and TRAF1 and TRAF2 gene expression, as well as protein–protein interaction in gastric epithelial AGS cells. We then demonstrated that pretreatment of cells with β-carotene significantly attenuates these effects. Our findings support the proposal that β-carotene has anti-cancer activity by reducing NADPH oxidase-mediated production of ROS, NF-κB activation and NF-κB-regulated TRAF1 and TRAF2 gene expression, and hyper-proliferation in AGS cells. We suggest that the consumption of β-carotene-enriched foods could decrease the incidence of H. pylori-associated gastric disorders.

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 The effect of Helicobacter pylori infection and different H. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0220636 ◽  
Author(s):  
Weronika Gonciarz ◽  
Agnieszka Krupa ◽  
Krzysztof Hinc ◽  
Michał Obuchowski ◽  
Anthony P Moran ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelial Cells ◽  
Proliferation And Apoptosis ◽  
H Pylori

Aberrant CpG Island Hypermethylation in Pediatric Gastric Mucosa in Association With Helicobacter pylori Infection

2011 ◽  
Vol 135 (6) ◽  
pp. 759-765
Author(s):  
So-Hyun Shin ◽  
Seog-Yun Park ◽  
Jae-Sung Ko ◽  
Nayoung Kim ◽  
Gyeong Hoon Kang
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Cpg Island ◽  
Methylation Status ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelial Cells ◽  
Infected Adult ◽  
H Pylori ◽  
Methylight Assay

Abstract Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion. Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues. Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples. Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P &lt; .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P &lt; .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P &lt; .05). Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.

scholarly journals Ceramide and Toll-Like Receptor 4 Are Mobilized into Membrane Rafts in Response to Helicobacter pylori Infection in Gastric Epithelial Cells

2012 ◽  
Vol 80 (5) ◽  
pp. 1823-1833 ◽  
Author(s):  
Dah-Yuu Lu ◽  
Hui-Chen Chen ◽  
Mei-Shiang Yang ◽  
Yuan-Man Hsu ◽  
Hwai-Jeng Lin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Lipid Rafts ◽  
Gastric Epithelial Cells ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Ags Cells ◽  
Content Type ◽  
Infected Cells ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection is thought to be involved in the development of several gastric diseases. TwoH. pylorivirulence factors (vacuolating cytotoxin A and cytotoxin-associated gene A) reportedly interact with lipid rafts in gastric epithelial cells. The role of Toll-like receptor (TLR)-mediated signaling in response toH. pyloriinfection has been investigated extensively in host cells. However, the receptor molecules in lipid rafts that are involved inH. pylori-induced innate sensing have not been well characterized. This study investigated whether lipid rafts play a role inH. pylori-induced ceramide secretion and TLR4 expression and thereby contribute to inflammation in gastric epithelial cells. We observed that both TLR4 and MD-2 mRNA and protein levels were significantly higher inH. pylori-infected AGS cells than in mock-infected cells. Moreover, significantly more TLR4 protein was detected in detergent-resistant membranes extracted fromH. pylori-infected AGS cells than in those extracted from mock-infected cells. However, this effect was attenuated by the treatment of cells with cholesterol-usurping agents, suggesting thatH. pylori-induced TLR4 signaling is dependent on cholesterol-rich microdomains. Similarly, the level of cellular ceramide was elevated and ceramide was translocated into lipid rafts afterH. pyloriinfection, leading to interleukin-8 (IL-8) production. Using the sphingomyelinase inhibitor imipramine, we observed thatH. pylori-induced TLR4 expression was ceramide dependent. These results indicate the mobilization of ceramide and TLR4 into lipid rafts byH. pyloriinfection in response to inflammation in gastric epithelial cells.

Human Gastric Epithelium Produces IL-4 and IL-4δ2 Isoform Only upon Helicobacter Pylori Infection

2007 ◽  
Vol 20 (4) ◽  
pp. 809-818 ◽  
Author(s):  
B. Orsini ◽  
J.R. Vivas ◽  
B. Ottanelli ◽  
A. Amedei ◽  
E. Surrenti ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Healthy Subjects ◽  
Fine Tuning ◽  
Gastric Epithelium ◽  
Gastric Epithelial Cells ◽  
H Pylori ◽  
Cag Pai

Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4δ2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island ( cag-PAI). IL-4 and IL-4δ2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SSI strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori-infected patients, and markedly reduced in cag-PAI-positive ones. IL-4δ2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-452 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SSI strain stimulation, whereas IL-4δ2 mRNA expression was detected in AGS co-cultured with either SSI or B128 strains. An inverse correlation was documented between IL-4 and IL-482 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-452, is expressed by gastric epithelium of healthy subjects, whereas IL-452 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4δ2 expression.

Helicobacter pylori infection activates NF-κB signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis

2003 ◽  
Vol 285 (6) ◽  
pp. G1171-G1180 ◽  
Author(s):  
Jung Mogg Kim ◽  
Joo Sung Kim ◽  
Hyun Chae Jung ◽  
Yu-Kyoung Oh ◽  
Hee-Young Chung ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Inos Expression ◽  
Helicobacter Pylori Infection ◽  
Inos Mrna ◽  
Gastric Epithelial Cells ◽  
Iκb Kinase ◽  
H Pylori

Helicobacter pylori infection induces apoptosis and inducible nitric oxide synthase (iNOS) expression in gastric epithelial cells. In this study, we investigated the effects of NF-κB activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-κB significantly increased caspase-3 activity and apoptosis in H. pylori-infected MKN-45 and Hs746T gastric epithelial cell lines as well as primary gastric epithelial cells. An NF-κB signaling pathway via NF-κB-inducing kinase and IκB kinase-β activation was found to be involved in the inhibition of apoptosis in H. pylori-infected gastric epithelial cells. In gastric epithelial cells transfected with retrovirus containing IκBα superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-κB. Moreover, a NO donor, S-nitroso- N-acetylpenicillamine (100 μM), decreased caspase-3 activity and apoptosis in NF-κB-suppressed cells infected with H. pylori. These results suggest that NF-κB activation may play a role in protecting gastric epithelial cells from H. pylori-induced apoptosis by upregulating endogenous iNOS.

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