scholarly journals Fucoidan from Sargassum hemiphyllum inhibits infection and inflammation of Helicobacter pylori

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo-Rui Chen ◽  
Wei-Ming Li ◽  
Tsung-Lin Li ◽  
Yi-Lin Chan ◽  
Chang-Jer Wu
Keyword(s):  
Drug Resistance ◽  
Helicobacter Pylori ◽  
Cell Model ◽  
Host Cells ◽  
Total Count ◽  
Gastric Adenoma ◽  
Antibiotic Failure ◽  
H Pylori ◽  
Sargassum Hemiphyllum

AbstractHaving infected by Helicobacter pylori, the infection often leads to gastritis, gastric ulcer, or even gastric cancer. The disease is typically treated with antibiotics as they used to effectively inhibit or kill H. pylori, thus reducing the incidence of gastric adenoma and cancer to significant extent. H. pylori, however, has developed drug resistance to many clinically used antibiotics over the years, highlighting the crisis of antibiotic failure during the H. pylori treatment. We report here that the fucoidan from Sargassum hemiphyllum can significantly reduce the infection of H. pylori without developing to drug resistance. Fucoidan appears to be a strong anti-inflammation agent as manifested by the RAW264.7 cell model examination. Fucoidan can prohibit H. pylori adhesion to host cells, thereby reducing the infection rate by 60%, especially in post treatment in the AGS cell model assay. Mechanistically, fucoidan intervenes the adhesion of BabA and AlpA of H. pylori significantly lowering the total count of H. pylori and the level of IL-6 and TNF-α in vivo. These results all converge on the same fact that fucoidan is an effective agent in a position to protect the stomach from the H. pylori infection by reducing both the total count and induced inflammation.

scholarly journals Fucoidan from Sargassum Hemiphyllum Inhibits Infection and Inflammation of Helicobacter Pylori

2021 ◽  
Author(s):  
Bo-Rui Chen ◽  
Wei-Ming Li ◽  
Tsung-Lin Li ◽  
Yi-Lin Chan ◽  
Chang-Jer Wu
Keyword(s):  
Drug Resistance ◽  
Helicobacter Pylori ◽  
Infection Rate ◽  
Cell Model ◽  
Host Cells ◽  
Total Count ◽  
Gastric Adenoma ◽  
H Pylori ◽  
Proper Functions

Abstract When infected by Helicobacter pylori, it often causes gastritis, gastric ulcer, or gastric cancer. Antibiotics are used to treat H. pylori infection, as they inhibit or kill H. pylori often ex-tending to reduce the incidences of gastric adenoma and cancer. However, H. pylori has developed drug resistance to many clinically used antibiotics over the years, thereby providing no warranty of successful treatment whenever H. pylori infection befalls. We report here that fucoidan from Sargassumhemiphyllum can effectively reduce infection of H. pylori without development of drug resistance. Fucoidan demonstrated a strong anti-inflammation activity in RAW264.7 cell model. Using AGS cell model, fucoidan decreased H. pylori adhesion to host cells and thus reduced its infection rate, especially in post-treatment where the infection rate was reduced to 40%. Mechanistically, fucoidan intervenes the proper functions of adhesion molecules BabA and AlpA of H. pylori. Moreover, fucoidan is able to significantly lower the total count of H. pylori and the levels of IL-6 and TNF-α in vivo. Added together, these convergent results suggest that fucoidan is an effective agent in a position to protect stomach from H. pylori infection by reducing its total count and induced inflammation.

scholarly journals Specific Entry of Helicobacter pylori into Cultured Gastric Epithelial Cells via a Zipper-Like Mechanism

2002 ◽  
Vol 70 (4) ◽  
pp. 2108-2120 ◽  
Author(s):  
Terry Kwok ◽  
Steffen Backert ◽  
Heinz Schwarz ◽  
Jürgen Berger ◽  
Thomas F. Meyer
Keyword(s):  
Helicobacter Pylori ◽  
Cell Model ◽  
Close Association ◽  
Host Cells ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Filamentous Actin ◽  
Ags Cells ◽  
Necrosis Factor Alpha ◽  
H Pylori

ABSTRACT Although Helicobacter pylori has generally been considered an extracellular pathogen, a number of in vitro infection experiments and biopsy examinations have shown that it is capable of occasionally entering mammalian host cells. Here, we characterized this entry process by using AGS cells as a host cell model. In gentamicin protection-invasion assays, the number of H. pylori colonies recovered was lower than that for Salmonella enterica serovar Typhimurium X22, Escherichia coli expressing InvA, and Yersinia enterocolitica YO:9 grown at 25°C but higher than that for Neisseria gonorrhoeae VP1 and Y. enterocolitica YO:9 grown at 37°C. At the ultrastructural level, the entry process was observed to occur via a zipper-like mechanism. Internalized H. pylori was bound in tight LAMP-1-containing vacuoles in close association with condensed filamentous actin and tyrosine phosphorylation signals. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, and calphostin C, an inhibitor of protein kinase C, both inhibited the entry of H. pylori in a sensitive and dose-dependent manner; however, the level of entry was enhanced by sodium vanadate, an inhibitor of tyrosine phosphatases and ATPases. Furthermore, the cytokine tumor necrosis factor alpha antagonized the entry of H. pylori into AGS cells. Collectively, these results demonstrate that the entry of H. pylori into AGS cells occurs via a zipper-like mechanism which involves various host signal transduction events.

scholarly journals TLR9 activation suppresses inflammation in response to Helicobacter pylori infection

2016 ◽  
Vol 311 (5) ◽  
pp. G852-G858 ◽  
Author(s):  
Matthew G. Varga ◽  
M. Blanca Piazuelo ◽  
Judith Romero-Gallo ◽  
Alberto G. Delgado ◽  
Giovanni Suarez ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Disease Risk ◽  
Host Cells ◽  
Dependent Manner ◽  
Wild Type ◽  
Host Genotype ◽  
Immunological Responses ◽  
Type Iv ◽  
H Pylori

Helicobacter pylori ( H. pylori) induces chronic gastritis in humans, and infection can persist for decades. One H. pylori strain-specific constituent that augments disease risk is the cag pathogenicity island. The cag island encodes a type IV secretion system (T4SS) that translocates DNA into host cells. Toll-like receptor 9 (TLR9) is an innate immune receptor that detects hypo-methylated CpG DNA motifs. In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo. H. pylori strain PMSS1 or its cagE − mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9 −/− C57BL/6 mice. PMSS1-infected Tlr9 −/− mice developed significantly higher levels of inflammation, despite similar levels of colonization density, compared with PMSS1-infected wild-type mice. These changes were cag dependent, as both mouse genotypes infected with the cagE − mutant only developed minimal inflammation. Tlr9 −/− genotypes did not alter the microbial phenotypes of in vivo-adapted H. pylori strains; therefore, we examined host immunological responses. There were no differences in levels of TH1 or TH2 cytokines in infected mice when stratified by host genotype. However, gastric mucosal levels of IL-17 were significantly increased in infected Tlr9 −/− mice compared with infected wild-type mice, and H. pylori infection of IL-17A −/− mice concordantly led to significantly decreased levels of gastritis. Thus loss of Tlr9 selectively augments the intensity of IL-17-driven immune responses to H. pylori in a cag T4SS-dependent manner. These results suggest that H. pylori utilizes the cag T4SS to manipulate the intensity of the host immune response.

scholarly journals Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression

2016 ◽  
Vol 84 (5) ◽  
pp. 1526-1535 ◽  
Author(s):  
Nele de Klerk ◽  
Lisa Maudsdotter ◽  
Hanna Gebreegziabher ◽  
Sunil D. Saroj ◽  
Beatrice Eriksson ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Binding Capacity ◽  
Host Cells ◽  
Gastric Epithelial Cells ◽  
Content Type ◽  
Effector Molecule ◽  
H Pylori

The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of whichLactobacillusspecies are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment ofHelicobacter pylorito host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogenH. pylori. In a screen withLactobacillusisolates, we found that only a few could reduce adherence ofH. pylorito gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act onH. pyloridirectly by an effector molecule that is released into the medium. This effector molecule acts onH. pyloriby inhibiting expression of the adhesin-encoding genesabA. Finally, we verified that inhibitory lactobacilli reducedH. pyloricolonization in anin vivomodel. In conclusion, certainLactobacillusstrains affect pathogen adherence by inhibitingsabAexpression and thereby reducingH. pyloribinding capacity.

scholarly journals Coupled Amino Acid Deamidase-Transport Systems Essential for Helicobacter pylori Colonization

2010 ◽  
Vol 78 (6) ◽  
pp. 2782-2792 ◽  
Author(s):  
Damien Leduc ◽  
Julien Gallaud ◽  
Kerstin Stingl ◽  
Hilde de Reuse
Keyword(s):  
Amino Acids ◽  
Helicobacter Pylori ◽  
Amino Acid ◽  
Nitrogen Sources ◽  
Host Cells ◽  
Transport Systems ◽  
Uptake System ◽  
Highly Active ◽  
H Pylori

ABSTRACT In addition to their classical roles as carbon or nitrogen sources, amino acids can be used for bacterial virulence, colonization, or stress resistance. We found that original deamidase-transport systems impact colonization by Helicobacter pylori, a human pathogen associated with gastric pathologies, including adenocarcinoma. We demonstrated that l-asparaginase (Hp-AnsB) and γ-glutamyltranspeptidase (Hp-γGT) are highly active periplasmic deamidases in H. pylori, producing ammonia and aspartate or glutamate from asparagine and glutamine, respectively. Hp-GltS was identified as a sole and specialized transporter for glutamate, while aspartate was exclusively imported by Hp-DcuA. Uptake of Gln and Asn strictly relies on indirect pathways following prior periplasmic deamidation into Glu and Asp. Hence, in H. pylori, the coupled action of periplasmic deamidases with their respective transporters enables the acquisition of Glu and Asp from Gln and Asn, respectively. These systems were active at neutral rather than acidic pH, suggesting their function near the host epithelial cells. We showed that Hp-DcuA, the fourth component of these novel deamidase-transport systems, was as crucial as Hp-γGT, Hp-AnsB, and Hp-GltS for animal model colonization. In conclusion, the pH-regulated coupled amino acid deamidase-uptake system represents an original optimized system that is essential for in vivo colonization of the stomach environment by H. pylori. We propose a model in which these two nonredundant systems participate in H. pylori virulence by depleting gastric or immune cells from protective amino acids such as Gln and producing toxic ammonia close to the host cells.

scholarly journals Antagonistic and Immunomodulant Effects of Two Probiotic Strains of Lactobacillus on Clinical Strains of Helicobacter pylori

2020 ◽  
Vol 9 ◽  
pp. 1794
Author(s):  
Somayyeh Taghizadeh ◽  
Tahereh Falsafi ◽  
Rouha Kasra Kermanshahi ◽  
Reihaneh Ramezani
Keyword(s):  
Helicobacter Pylori ◽  
Cell Model ◽  
Host Cells ◽  
Macrophage Cell ◽  
Cell Free Supernatant ◽  
Probiotic Strains ◽  
Ifn Γ ◽  
Probiotic Lactobacilli ◽  
H Pylori

Background: The present study aimed to evaluate the in vitro and in situ antagonistic effects of Lactobacillus probiotic strains on clinical strains of Helicobacter pylori . Also to investigate their immunomodulation effects on a macrophage cell model. Materials and Methods: Anti-microbial effects of probiotic lactobacilli against H. pylori was assessed using the well and disk diffusion methods. Effects of lactobacilli probiotics strains, as well as their cell-free supernatant on adhesion of H. pylori to MKN-45 gastric epithelial cells, were examined in their presence and absence. Immunomodulation effects of probiotic lactobacilli were performed using the U937 macrophage cell model. Incubation of host cells with probiotics and their cell-free supernatants with cultured host cells was performed in different optimized conditions. The supernatant of host cells cultured in their presence and absence was used for cytokines measurement. Results: Two probiotics‏, Lactobacillus acidophilus ATCC4356, and Lactobacillus rhamnosus PTCC1607, could inhibit the growth of clinical H. pylori in vitro. They could also inhibit attachment of H. pylori to MKN-45 cells. Cell-free supernatant of L. acidophilus had a stimulating effect on the production of Interferon-gamma (IFN-γ) by U937 cells. Conclusion: The present study demonstrates that, L. acidophilus ATCC4356 and L. rhamnosus PTCC1607 probiotic strains can inhibit the growth of clinical H. pylori in vitro. Treatment of U937 with alive H. pylori plus cell-free supernatant of L. acidophilus, have a significantly higher capacity to stimulate IFN-γ production than H. pylori alone. So, the metabolite (s) of this probiotic may have an immunomodulatory effect in immune response versus H. pylori. [GMJ.2020;9:e1794]

scholarly journals Helicobacter pylori Infection Introduces DNA Double-Strand Breaks in Host Cells

2014 ◽  
Vol 82 (10) ◽  
pp. 4182-4189 ◽  
Author(s):  
Katsuhiro Hanada ◽  
Tomohisa Uchida ◽  
Yoshiyuki Tsukamoto ◽  
Masahide Watada ◽  
Nahomi Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Genomic Instability ◽  
Double Strand Breaks ◽  
Host Cells ◽  
Dna Double Strand Breaks ◽  
Content Type ◽  
Strand Breaks ◽  
H Pylori

ABSTRACTGastric cancer is an inflammation-related malignancy related to long-standing acute and chronic inflammation caused by infection with the human bacterial pathogenHelicobacter pylori. Inflammation can result in genomic instability. However, there are considerable data thatH. pyloriitself can also produce genomic instability both directly and through epigenetic pathways. Overall, the mechanisms ofH. pylori-induced host genomic instabilities remain poorly understood. We used microarray screening ofH. pylori-infected human gastric biopsy specimens to identify candidate genes involved inH. pylori-induced host genomic instabilities. We found upregulation ofATMexpressionin vivoin gastric mucosal cells infected withH. pylori. Using gastric cancer cell lines, we confirmed that theH. pylori-related activation of ATM was due to the accumulation of DNA double-strand breaks (DSBs). DSBs were observed following infection with bothcagpathogenicity island (PAI)-positive and -negative strains, but the effect was more robust withcagPAI-positive strains. These results are consistent with the fact that infections with bothcagPAI-positive and -negative strains are associated with gastric carcinogenesis, but the risk is higher in individuals infected withcagPAI-positive strains.

scholarly journals Strain-specific suppression of microRNA-320 by carcinogenic Helicobacter pylori promotes expression of the antiapoptotic protein Mcl-1

2013 ◽  
Vol 305 (11) ◽  
pp. G786-G796 ◽  
Author(s):  
Jennifer M. Noto ◽  
M. Blanca Piazuelo ◽  
Rupesh Chaturvedi ◽  
Courtney A. Bartel ◽  
Elizabeth J. Thatcher ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Human Subjects ◽  
Gastric Carcinogenesis ◽  
Host Cells ◽  
Dependent Manner ◽  
Antiapoptotic Protein ◽  
Small Noncoding Rnas ◽  
Increased Risk ◽  
H Pylori

Helicobacter pylori is the strongest risk factor for gastric cancer, and strains harboring the cag pathogenicity island, which translocates the oncoprotein CagA into host cells, further augment cancer risk. We previously reported that in vivo adaptation of a noncarcinogenic H. pylori strain (B128) generated a derivative strain (7.13) with the ability to induce adenocarcinoma, providing a unique opportunity to define mechanisms that mediate gastric carcinogenesis. MicroRNAs (miRNAs) are small noncoding RNAs that regulate expression of oncogenes or tumor suppressors and are frequently dysregulated in carcinogenesis. To identify miRNAs and their targets involved in H. pylori-mediated carcinogenesis, miRNA microarrays were performed on RNA isolated from gastric epithelial cells cocultured with H. pylori strains B128, 7.13, or a 7.13 cagA − isogenic mutant. Among 61 miRNAs differentially expressed in a cagA-dependent manner, the tumor suppressor miR-320 was significantly downregulated by strain 7.13. Since miR-320 negatively regulates the antiapoptotic protein Mcl-1, we demonstrated that H. pylori significantly induced Mcl-1 expression in a cagA-dependent manner and that suppression of Mcl-1 results in increased apoptosis. To extend these results, mice were challenged with H. pylori strain 7.13 or its cagA − mutant; consistent with cell culture data, H. pylori induced Mcl-1 expression in a cagA-dependent manner. In human subjects, cag + strains induced significantly higher levels of Mcl-1 than cag − strains, and Mcl-1 expression levels paralleled the severity of neoplastic lesions. Collectively, these results indicate that H. pylori suppresses miR-320, upregulates Mcl-1, and decreases apoptosis in a cagA-dependent manner, which likely confers an increased risk for gastric carcinogenesis.

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 Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

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