Implication of Nf-κB in Helicobacter Pylori -Associated Gastritis

Isomoto, Hajime; Mizuta, Yohei; Miyazaki, Masanobu; Takeshima, Fuminao; Omagari, Katsuhisa; Murase, Kunihiko; Nishiyama, Toshihiko; Inoue, Kenichiro; Murata, Ikuo; Kohno, Shigeru

doi:10.1111/j.1572-0241.2000.02304.x

Cited by 52 publications

(38 citation statements)

References 33 publications

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“…The mechanisms and signaling pathways involved in H. pylori induction of NF-B responses in human GECs have been studied in great detail in vitro, yet the in vivo relevance of these observations has only rarely been investigated. Activated NF-B complexes were detected by immunohistochemistry within the gastric mucosa of individuals chronically infected with H. pylori (17,18,46). Consistent with the work presented here (Fig.…”

Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 81%

“…Consistent with the work presented here (Fig. 5), most of the activated NF-B complexes in those studies were associated with the nuclei of epithelial cells (17,18,46). Although one report specifically referred to NF-B activation in antral GECs, only antral samples were analyzed in that study (46).…”

Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 76%

“…Although one report specifically referred to NF-B activation in antral GECs, only antral samples were analyzed in that study (46). As found here, other workers reported NF-B activation in GECs throughout the body and antral tissues of H. pylori-infected individuals (17,18).…”

Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557mentioning

confidence: 70%

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NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Ferrero¹,

Avé²,

Ndiaye

et al. 2008

Infect Immun

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Nuclear factor B (NF-B) plays a key regulatory role in host cell responses to Helicobacter pylori infection in humans. Although mice are routinely used as a model to study H. pylori pathogenesis, the role of NF-B in murine cell responses to helicobacters has not been studied in detail. We thus investigated the abilities of different Helicobacter isolates to induce NF-B-dependent responses in murine gastric epithelial cells (GECs) and in transgenic mice harboring an NF-B-responsive lacZ reporter gene. H. pylori and Helicobacter felis strains up-regulated the synthesis in mouse GECs of the NF-B-dependent chemokines KC (CXCL1) and MIP-2 (CXCL2). These responses were cag pathogenicity island (cagPAI) independent and could be abolished by pretreatment with a pharmacological inhibitor of NF-B. Consistent with the in vitro data, experimental Helicobacter infection of transgenic mice resulted in increased numbers of GECs with nuclear ␤-galactosidase activity, which is indicative of specific NF-B activation. The numbers of ␤-galactosidase-positive cells in mice were significantly increased at day 1 postinoculation with wild-type H. pylori strains harboring or not harboring a functional cagPAI, compared to naive animals (P ‫؍‬ 0.007 and P ‫؍‬ 0.04, respectively). Strikingly, however, no differences were observed in the levels of gastric NF-B activation at day 1 postinoculation with H. felis or at day 30 or 135 postinoculation with H. pylori. This work demonstrates for the first time the induction of NF-B activation within gastric mucosal cells during acute H. pylori infection. Furthermore, the data suggest that helicobacters may be able to regulate NF-B signaling during chronic infection.

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Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 81%

Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 76%

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NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Ferrero¹,

Avé²,

Ndiaye

et al. 2008

Infect Immun

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“…The mechanism by which serum eliminates the apoptotic activity of H. pylori is unclear. However, an antiapoptotic substance(s) expressed by H. pylori in response to serum would likely be involved, since H. pylori infection could stimulate potential antiapoptotic signals, including tyrosine kinases (2,46,58,(63)(64)(65)68), protein kinase C (5,6,69), and the transcription factor NF-B (25,29,32,39,48,57). The ability of H. pylori to stimulate antiapoptotic pathways is not surprising, since there appears to be no obvious benefit for H. pylori from rapid host cell killing, which would result in the loss of colonization sites.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Signaling Pathway Activated by Helicobacter pylori Infection and Increase of Apoptosis-Inducing Activity under Serum-Starved Conditions

et al. 2001

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The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.

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“…In vitro studies have revealed that infection with H. pylori induces the expression of chemokines by the activation of NF-B in mucosal epithelial cells and then facilitates inflammatory responses (3,10,14). On the other hand, we have reported that MT deficiency affects redox status, activating NF-B-dependent gene expression (32).…”

mentioning

confidence: 99%

Metallothionein is a crucial protective factor againstHelicobacter pylori-induced gastric erosive lesions in a mouse model

Mita¹,

Satoh²,

Shimada³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Infection with the gastric pathogen Helicobacter pylori ( H. pylori) causes chronic gastritis, peptic ulcer, and gastric adenocarcinoma. These diseases are associated with production of reactive oxygen species (ROS) from infiltrated macrophages and neutrophiles in inflammatory sites. Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that can act not only as a metal-binding protein, but also as a ROS scavenger. In the present study, we examined the role of MT in the protection against H. pylori-induced gastric injury using MT-null mice. Female MT-null and wild-type mice were challenged with H. pylori SS1 strain, and then histological changes were evaluated with the updated Sydney grading system at 17 and 21 wk after challenge. Although the colonization efficiency of H. pylori was essentially the same for MT-null and wild-type mice, the scores of activity of inflammatory cells were significantly higher in MT-null mice than in wild-type mice at 17 wk after challenge. Histopathological examination revealed erosive lesions accompanied by infiltration of inflammatory cells in the infected MT-null mice but not in wild-type mice. Furthermore, activation of NF-κB and expression of NF-κB-mediated chemokines such as macrophage inflammatory protein-1α and monocytes chemoattractant protein-1 in gastric cells were markedly higher in MT-null mice than in wild-type mice. These results suggest that MT in the gastric mucosa might play an important role in the protection against H. pylori-induced gastric ulceration.

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Implication of Nf-κB in Helicobacter Pylori -Associated Gastritis

Abstract: In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-kappaB. In these cells, activated NF-kappaB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.

Cited by 52 publications

References 33 publications

NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Apoptotic Signaling Pathway Activated by Helicobacter pylori Infection and Increase of Apoptosis-Inducing Activity under Serum-Starved Conditions

Metallothionein is a crucial protective factor againstHelicobacter pylori-induced gastric erosive lesions in a mouse model

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