scholarly journals Helicobacter pylori Outer Membrane Vesicles Modulate Proliferation and Interleukin-8 Production by Gastric Epithelial Cells

2003 ◽  
Vol 71 (10) ◽  
pp. 5670-5675 ◽  
Author(s):  
Salim Ismail ◽  
Mark B. Hampton ◽  
Jacqueline I. Keenan
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Strain Differences ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Interleukin 8 ◽  
Low Grade ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori infection, which is always associated with gastritis, can progress to ulceration or malignancy. The diversity in clinical outcomes is partly attributed to the expression of virulence factors and adhesins by H. pylori. However, H. pylori may not have to adhere to the epithelium to cause gastritis. We hypothesize that outer membrane vesicles (OMV), which are constantly shed from the surface of H. pylori, play a role as independent activators of host cell responses. In this study, we found that low doses of OMV from cag PAI+ toxigenic and cag PAI− nontoxigenic strains increased proliferation of AGS gastric epithelial cells. At higher doses, we detected growth arrest, increased toxicity, and interleukin-8 (IL-8) production. The only strain differences detected were vacuolation with the toxigenic strain and higher levels of IL-8 production with OMV from the cag PAI− nontoxigenic strain. In summary, we suggest that constitutively shed OMV play a role in promoting the low-grade gastritis associated with H. pylori infection.

scholarly journals Uptake of Helicobacter pylori Outer Membrane Vesicles by Gastric Epithelial Cells

2010 ◽  
Vol 78 (12) ◽  
pp. 5054-5061 ◽  
Author(s):  
Heather Parker ◽  
Kenny Chitcholtan ◽  
Mark B. Hampton ◽  
Jacqueline I. Keenan
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Mutant Strain ◽  
Membrane Vesicles ◽  
Human Stomach ◽  
Outer Membrane Vesicles ◽  
Gastric Epithelial Cells ◽  
Isogenic Mutant Strain ◽  
H Pylori

ABSTRACT Helicobacter pylori bacteria colonize the human stomach where they stimulate a persistent inflammatory response. H. pylori is considered noninvasive; however, lipopolysaccharide (LPS)-enriched outer membrane vesicles (OMV), continuously shed from the surface of this bacterium, are observed within gastric epithelial cells. The mechanism of vesicle uptake is poorly understood, and this study was undertaken to examine the roles of bacterial VacA cytotoxin and LPS in OMV binding and cholesterol and clathrin-mediated endocytosis in vesicle uptake by gastric epithelial cells. OMV association was examined using a fluorescent membrane dye to label OMV, and a comparison was made between the associations of vesicles from a VacA+ strain and OMV from a VacA− isogenic mutant strain. Within 20 min, essentially all associated OMV were intracellular, and vesicle binding appeared to be facilitated by the presence of VacA cytotoxin. Uptake of vesicles from the VacA+ strain was inhibited by H. pylori LPS (58% inhibition with 50 μg/ml LPS), while uptake of OMV from the VacA− mutant strain was less affected (25% inhibition with 50 μg/ml LPS). Vesicle uptake did not require cholesterol. However, uptake of OMV from the VacA− mutant strain was inhibited by a reduction in clathrin-mediated endocytosis (42% with 15 μg/ml chlorpromazine), while uptake of OMV from the VacA+ strain was less affected (25% inhibition with 15 μg/ml chlorpromazine). We conclude that VacA toxin enhances the association of H. pylori OMV with cells and that the presence of the toxin may allow vesicles to exploit more than one pathway of internalization.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Identification of Functional Interactome of Gastric Cancer Cells with Helicobacter pylori Outer Membrane Protein HpaA by HPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ruyue Fan ◽  
Xiurui Han ◽  
Di Xiao ◽  
Lihua He ◽  
Yanan Gong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Cell Lines ◽  
Outer Membrane Protein ◽  
Regulation Of Transcription ◽  
Gastric Epithelial Cells ◽  
H Pylori

HpaA as an outer membrane protein of Helicobacter pylori (H. pylori) plays a significant role in the adhesion to the human stomach, but the functional relation between HpaA and gastric epithelial cells is still not clear. To screen the interaction between HpaA and cellular proteins in gastric epithelial cells, the HpaA protein from H. pylori 26695 fused with a tag (6× His) was expressed and purified successfully, the secondary structure was estimated by the Circular Dichroism (CD) spectrum, and the purified recombinant protein was used to perform the pull-down assays with gastric cancer cell lines (AGS and SGC-7901) lysates, respectively. The pull-down proteins were identified by high-performance liquid chromatography tandem mass spectrometry system (HPLC-MS/MS). A total of 9 and 13 proteins related were analyzed from AGS and SGC-7901 cell lysates, respectively. ANXA2 was considered as putative HpaA functional partner discovered from lysates of both cell lines with high score and coverage. It is hypothesized that HpaA may be involved in the biological process of regulation of transcription and nucleic acid metabolism during the adhesion of H. pylori to human gastric epithelial cells, and HpaA-binding proteins also be used as targets for the development of antiadhesion drugs against H. pylori.

scholarly journals Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

2021 ◽  
Vol 22 (21) ◽  
pp. 11583
Author(s):  
Rossella Grande ◽  
Simone Carradori ◽  
Valentina Puca ◽  
Irene Vitale ◽  
Andrea Angeli ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Bacterial Resistance ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Peptic Ulcers ◽  
Carbonic Anhydrases ◽  
Biofilm Production ◽  
Isoform Selectivity ◽  
H Pylori

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

scholarly journals The Helicobacter pylori Urease B Subunit Binds to CD74 on Gastric Epithelial Cells and Induces NF-κB Activation and Interleukin-8 Production

2006 ◽  
Vol 74 (2) ◽  
pp. 1148-1155 ◽  
Author(s):  
Ellen J. Beswick ◽  
Irina V. Pinchuk ◽  
Kyle Minch ◽  
Giovanni Suarez ◽  
Johanna C. Sierra ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Fibroblast Cell ◽  
Surface Proteins ◽  
Interleukin 8 ◽  
Gastric Epithelial Cells ◽  
Bacterial Surface ◽  
B Subunit ◽  
H Pylori ◽  
Urease B Subunit

ABSTRACT The pathogenesis associated with Helicobacter pylori infection is the result of both bacterial factors and the host response. We have previously shown that H. pylori binds to CD74 on gastric epithelial cells. In this study, we sought to identify the bacterial protein responsible for this interaction. H. pylori urease from a pool of bacterial surface proteins was found to coprecipitate with CD74. To determine how urease binds to CD74, we used recombinant urease A and B subunits. Recombinant urease B was found to bind directly to CD74 in immunoprecipitation and flow cytometry studies. By utilizing both recombinant urease subunits and urease B knockout bacteria, the urease B-CD74 interaction was shown to induce NF-κB activation and interleukin-8 (IL-8) production. This response was decreased by blocking CD74 with monoclonal antibodies. Further confirmation of the interaction of urease B with CD74 was obtained using a fibroblast cell line transfected with CD74 that also responded with NF-κB activation and IL-8 production. The binding of the H. pylori urease B subunit to CD74 expressed on gastric epithelial cells presents a novel insight into a previously unrecognized H. pylori interaction that may contribute to the proinflammatory immune response seen during infection.

scholarly journals Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

2020 ◽  
Vol 8 (9) ◽  
pp. 1328 ◽  
Author(s):  
Miroslaw Jarzab ◽  
Gernot Posselt ◽  
Nicole Meisner-Kober ◽  
Silja Wessler
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Current Knowledge ◽  
Membrane Vesicles ◽  
Bacterial Pathogenesis ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
H Pylori

Persistent infections with the human pathogen Helicobacter pylori (H. pylori) have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of H. pylori is determined by a complicated network of manifold mechanisms of pathogen–host interactions, which involves a coordinated interplay of H. pylori pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from H. pylori and their implication in bacterial pathogenesis is not well developed. In this review, we summarize the current knowledge on H. pylori-derived OMVs.

scholarly journals Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR–IκB Kinase–NF-κB Pathways in Dendritic Cells

2016 ◽  
Vol 84 (8) ◽  
pp. 2162-2174 ◽  
Author(s):  
Su Hyuk Ko ◽  
Da Jeong Rho ◽  
Jong Ik Jeon ◽  
Young-Jeon Kim ◽  
Hyun Ae Woo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Dendritic Cells ◽  
Outer Membrane ◽  
Heme Oxygenase ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Heme Oxygenase 1 ◽  
Content Type ◽  
Iκb Kinase ◽  
H Pylori

Helicobacter pylorisheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses againstH. pylori, and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. AlthoughH. pylori-derived OMVs may contribute to the pathogenesis ofH. pyloriinfection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role ofH. pylori-derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crudeH. pyloriOMVs upregulated HO-1 expression. Crude OMVs obtained from acagA-negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. CrudeH. pyloriOMVs activated signals of transcription factors such as NF-κB, AP-1, and Nrf2. Suppression of NF-κB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV-induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IκB kinase (IKK), NF-κB, and HO-1 expression in crude OMV-exposed DCs. These results suggest thatH. pylori-derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR–IKK–NF-κB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses inH. pyloriinfection.

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