TNFα induced by H. Pylori phosphorylates JNK pathway which may induce apoptosis in gastric mucosal cells

1998 ◽  
Vol 114 ◽  
pp. A1168
Author(s):  
A. Nagahara ◽  
H. Miwa ◽  
M. Hirose ◽  
H. Misawa ◽  
M. Kawabe ◽  
...  
Keyword(s):  
Gastric Mucosal Cells ◽  
Jnk Pathway ◽  
Mucosal Cells ◽  
H Pylori

Helicobacter pylorilipopolysaccharide induces apoptosis of cultured guinea pig gastric mucosal cells

2001 ◽  
Vol 281 (3) ◽  
pp. G726-G734 ◽  
Author(s):  
Tsukasa Kawahara ◽  
Shigetada Teshima ◽  
Yuki Kuwano ◽  
Ayuko Oka ◽  
Kyoichi Kishi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cytochrome C ◽  
Guinea Pig ◽  
Primary Cultures ◽  
Specific Inhibitor ◽  
Caspase 8 ◽  
Cytochrome C Release ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells ◽  
H Pylori

Helicobacter pylori lipopolysaccharide (LPS) is generally accepted as a low-toxicity virulence. Primary cultures of guinea pig gastric mucosal cells expressed the Toll-like receptor 4 and were sensitive to H. pylori LPS as well as Escherichia coli LPS. H. pylori LPS stimulated phosphorylation of transforming growth factor-β-activated kinase 1 (TAK1), TAK1-binding protein 1 (TAB1), and c-Jun NH2-terminal kinase (JNK) 2. H. pylori LPS at >2.1 endotoxin unit/ml (>1 ng/ml) activated caspase-8, stimulated cytochrome c release from mitochondria, and subsequently activated caspases-9 and -3, leading to apoptosis. Epidermal growth factor blocked all of these apoptotic processes and inhibited apoptosis, whereas it did not modify the phosphorylation of TAK1, TAB1, and JNK2. A comparatively specific inhibitor of caspase-8 or -9 blocked apoptosis, whereas cytochrome c release was prevented only with a caspase-8-like inhibitor. Our results suggest that caspase-8 and mitochondria may play crucial roles in H. pylori LPS-induced apoptosis and that this accelerated apoptosis may be involved in abnormal cell turnover of H. pylori-infected gastric mucosa.

Ecabet sodium inhibitsHelicobacter pylorilipopolysaccharide-induced activation of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells

2005 ◽  
Vol 288 (2) ◽  
pp. G300-G307 ◽  
Author(s):  
Kenji Kusumoto ◽  
Tsukasa Kawahara ◽  
Yuki Kuwano ◽  
Shigetada Teshima-Kondo ◽  
Kyoko Morita ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Nadph Oxidase ◽  
Transforming Growth Factor ◽  
Polyacrylamide Gel Electrophoresis ◽  
Northern Hybridization ◽  
Gastric Mucosal Cells ◽  
Ecabet Sodium ◽  
Nadph Oxidase 1 ◽  
Mucosal Cells ◽  
H Pylori

Helicobacter pylori LPS activates a homolog of gp91phox, NADPH oxidase 1 (Nox1), in guinea pig gastric mucosal cells cultured in 10% FBS-containing medium. RT-PCR and Northern hybridization demonstrated that H. pylori LPS stimulated expression of Nox1 and a novel p47phoxhomolog (Noxo1) mRNAs with a peak at 4 h, followed by upregulation of superoxide anion (O2−) generation. Pretreatment with 10 mg/ml of a nonabsorbable antigastric ulcer drug, ecabet sodium (ecabet), completely blocked these two mRNA expressions and the upregulation of O2−production. Under low (0.1%)-FBS conditions, H. pylori LPS predominantly caused apoptosis of the cells. Ecabet completely blocked the LPS-triggered phosphorylation of transforming growth factor-β-activated kinase 1 (TAK1) and TAK1-binding protein 1, activation of caspase 8, loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase 3, and appearance of apoptotic cells. In contrast, ecabet had no effect on ethanol- or etoposide-initiated apoptosis. The ecabet-pretreated cells exhibited the responsiveness to H. pylori LPS, similarly as untreated control cells did, when ecabet was removed by washing before the addition of H. pylori LPS. Incubation of H. pylori LPS with ecabet eliminated the toxic effects of the LPS, and nondenatured polyacrylamide gel electrophoresis indicated the formation of higher molecular mass complexes between H. pylori LPS and ecabet, suggesting that ecabet may interact with H. pylori LPS and block the activation of Toll-like receptor 4 (TLR4). Our results suggest that ecabet may suppress TLR4-mediated inflammation or accelerated apoptosis caused H. pylori infection.

NSAIDs counteractH. pyloriVacA toxin-induced cell vacuolation in MKN 28 gastric mucosal cells

2002 ◽  
Vol 283 (3) ◽  
pp. G511-G520 ◽  
Author(s):  
Vittorio Ricci ◽  
Barbara A. Manzo ◽  
Concetta Tuccillo ◽  
Patrice Boquet ◽  
Ulderico Ventura ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Mucosal Injury ◽  
Channel Activity ◽  
Cell Binding ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells ◽  
Chloride Channel Blocker ◽  
Inflammatory Drugs ◽  
H Pylori ◽  
The Relationship

The relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori-induced gastric mucosal injury is still under debate. VacA toxin is an important H. pylori virulence factor that causes cytoplasmic vacuolation in cultured cells. Whether and how NSAIDs affect VacA-induced cytotoxicity is unclear. This study was designed to evaluate the effect of NSAIDs on H. pylori VacA toxin-induced cell vacuolation in human gastric mucosal cells in culture (MKN 28 cell line). Our data show that 1) NSAIDs (indomethacin, aspirin, and NS-398) inhibit VacA-induced cell vacuolation independently of inhibition of cell proliferation and prostaglandin synthesis; 2) NSAIDs impair vacuole development/maintenance without affecting cell binding and internalization of VacA; and 3) NSAIDs, as well as the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid, also inhibit cell vacuolation induced by ammonia. We thus hypothesize that NSAIDs might protect MKN 28 cells against VacA-induced cytotoxicity by inhibiting VacA channel activity required for vacuole genesis.

scholarly journals L-GLUTAMINE ERADICATES HELICOBACTER PYLORI GASTRITIS: A NOVEL CASE REPORT

2017 ◽  
Vol 10 (10) ◽  
pp. 13
Author(s):  
Balaji Ommurugan ◽  
Amita Priya
Keyword(s):  
Helicobacter Pylori ◽  
Sports Medicine ◽  
Gastrointestinal Diseases ◽  
Epithelial Proliferation ◽  
Gastric Mucosal Cells ◽  
First Case ◽  
Mucosal Cells ◽  
H Pylori ◽  
Common Infection ◽  
Helicobacter Pylori Gastritis

  Helicobacter pylori is the most common infection causing gastrointestinal diseases in the developing countries. It causes oxidative damage to gastric mucosal cells thereby altering the epithelial proliferation of these cells. With proton pump inhibitors and antibiotics being the mainstay in the management of symptoms, preclinical and clinical research is making inroads with novel therapeutic innovations to target the bacterium with the help of antioxidants. Hence, we report the first case of the treatment and eradication of H. pylori using L-glutamine, a sports medicine supplement with high antioxidant potential.

Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells

2005 ◽  
Vol 288 (2) ◽  
pp. C450-C457 ◽  
Author(s):  
Tsukasa Kawahara ◽  
Motoyuki Kohjima ◽  
Yuki Kuwano ◽  
Hisano Mino ◽  
Shigetada Teshima-Kondo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Guinea Pig ◽  
Nadph Oxidase ◽  
Primary Cultures ◽  
Transcriptional Level ◽  
Type I ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells ◽  
H Pylori ◽  
Constitutively Active

Primary cultures of guinea pig gastric mucosal cells express NADPH oxidase 1 (Nox1), a homolog of gp91 phox, and produce superoxide anion (O2−) at a rate of ∼100 nmol·mg protein−1·h−1 in response to Helicobacter pylori ( H. pylori) lipopolysaccharide (LPS) from virulent type I strains. The upregulated O2− production also enhances H. pylori LPS-stimulated tumor necrosis factor-α or cyclooxygenase-2 mRNA expression, which suggests a potential role for Nox1 in the pathogenesis of H. pylori-associated diseases. The H. pylori LPS-stimulated O2− production in cultured gastric mucosal cells was inhibited by actinomycin D as well as cycloheximide, suggesting that the induction is regulated at the transcriptional level. The LPS treatment not only increased the Nox1 mRNA to a greater extent but also induced expression of the message-encoding, Nox-organizing protein 1 (NOXO1), a novel p47 phox homolog required for Nox1 activity. In addition, H. pylori LPS activated Rac1; i.e., it converted Rac1 to the GTP-bound state. A phosphoinositide 3-kinase inhibitor, LY-294002, blocked H. pylori LPS-induced Rac1 activation and O2− generation without interfering with the expression of Nox1 and NOXO1 mRNA. O2− production inhibited by LY-294002 was completely restored by transfection of an adenoviral vector encoding a constitutively active Rac1 but not an inactive Rac1 or a constitutively active Cdc42. These findings indicate that Rac1 plays a crucial role in Nox1 activation. Thus the H. pylori LPS-stimulated O2− production in gastric mucosal cells appears to require two distinct events: 1) transcriptional upregulation of Nox1 and NOXO1 and 2) activation of Rac1.

scholarly journals Helicobacter pylori Infection of Human and Murine Primary Gastric Cells

2004 ◽  
Vol 72 (9) ◽  
pp. 5464-5469 ◽  
Author(s):  
Marguerite Clyne ◽  
Brendan Drumm
Keyword(s):  
Animal Model ◽  
Helicobacter Pylori ◽  
Helicobacter Pylori Infection ◽  
Gastric Mucosal Cells ◽  
Cell Lysates ◽  
Gastric Cells ◽  
Mucosal Cells ◽  
H Pylori

ABSTRACT The effect of Helicobacter pylori infection on human and murine primary gastric cells was determined. CagA was phosphorylated following adherence of H. pylori to primary human gastric cells. However, it did not adhere to human primary duodenal cells or murine gastric cells, and CagA could not be detected in cell lysates. Identification of an easily available animal model of infection in which the organism adheres to gastric mucosal cells would enhance studies of the virulence of H. pylori.

scholarly journals Ghrelin Protection against Lipopolysaccharide-Induced Gastric Mucosal Cell Apoptosis Involves Constitutive Nitric Oxide Synthase-Mediated Caspase-3 S-Nitrosylation

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Bronislaw L. Slomiany ◽  
Amalia Slomiany
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Caspase 3 ◽  
Mucosal Cell ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells ◽  
H Pylori ◽  
Constitutive Nitric Oxide Synthase ◽  
Induced Changes ◽  
Oxide Synthase

Ghrelin, a peptide hormone produced mainly in the stomach, has emerged as an important modulator of the inflammatory responses that are of significance to the maintenance of gastric mucosal integrity. Here, we report on the role of ghrelin in controlling the apoptotic processes induced in gastric mucosal cells byH. pylorilipopolysaccharide (LPS). The countering effect of ghrelin on the LPS-induced mucosal cell apoptosis was associated with the increase in constitutive nitric oxide synthase (cNOS) activity, and the reduction in caspase-3 and inducible nitric oxide synthase (NOS-2). The loss in countering effect of ghrelin on the LPS-induced changes in apoptosis and caspase-3 activity was attained with Src kinase inhibitor, PP2, as well as Akt inhibitor, SH-5, and cNOS inhibitor, L-NAME. Moreover, the effect of ghrelin on the LPS-induced changes in cNOS activity was reflected in the increased cNOS phosphorylation that was sensitive to SH-5. Furthermore, the ghrelin-induced up-regulation in cNOS activity was associated with the increase in caspase-3 S-nitrosylation that was susceptible to the blockage by L-NAME. Therefore, ghrelin protection of gastric mucosal cells againstH. pyloriLPS-induced apoptosis involves Src/Akt-mediated up-regulation in cNOS activation that leads to the apoptotic signal inhibition through the NO-induced caspase-3 S-nitrosylation.

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