IL-1β–Induced apoptosis in rat gastric enterochromaffin-like cells is mediated by iNOS, NF-κB, and Bax protein

Mahr, Sabine; Neumayer, Nina; Gerhard, Markus; Classen, Meinhard; Prinz, Christian

doi:10.1016/s0016-5085(00)70257-5

Cited by 42 publications

(23 citation statements)

References 49 publications

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“…Simultaneous incubation with L -NMMA and TNF-α was found to inhibit TNF-α-induced cell death completely (n = 3, p < 0.001). Similar to previous results [1], L -NMMA alone did not have an effect on ECL cell apoptosis (not shown).…”

Section: Resultssupporting

confidence: 92%

“…ECL cells in vitro and in vivo may be susceptible only at a certain time point during their life cycle (approximately 60 days). Second, TNF-α induction of ECL cell death was significantly higher than the apoptotic rate seen after incubation with the cytokine IL-1β (100 pg/ml, 24 h) in our previous studies [1]. With regard to IL-1β, the physiological importance of this cytokine has already been documented by showing that IL-1β impairs histamine release completely [2].…”

Section: Discussionmentioning

confidence: 81%

“…The stomach, however, is frequently infected with the bacterium Helicobacter pylori , leading to increased mucosal levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α or interleukin (IL)-1β. These cytokines are released in the gastric mucosa from human monocytes and macrophages and may also influence the secretory and proliferative response of ECL cells [1]. …”

Section: Introductionmentioning

confidence: 99%

“…These studies underlined that IL-1β induces programmed cell death of ECL cells via expression of inducible nitric oxide (NO) synthase (iNOS) and bax protein [1]. IL-1β-induced apoptosis of ECL cells may explain the clinical observation that Helicobacter pylori- positive patients have significantly lower gastric histamine concentrations and histidine decarboxylase (HDC) activity than H. pylori- negative subjects [3, 4, 5].…”

Section: Introductionmentioning

confidence: 99%

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Tumor Necrosis Factor-Alpha Effects on Rat Gastric Enterochromaffin-Like Cells

Huber

Zanner²,

Pohlinger³

et al. 2002

Digestion

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Gastric enterochromaffin-like (ECL) cells are histamine-producing cells in the gastric epithelium which are responsible for the peripheral regulation of acid secretion. The gastric mucosa is frequently infected with Helicobacter pylori, leading to increased levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). The aim of our current study was to identify the effect of TNF-α on programmed cell death. ECL cells were isolated from the rat corpus mucosa to a purity >90%. TNF receptor and adapter protein presence were determined using RT-PCR, Western blot and immunocytochemistry. Apoptosis was measured by Tdt-mediated dUTP nick end labeling reaction and by DNA fragmentation based ELISA. Isolated ECL cells were found to express the TNF receptor p55 and IFN-γ receptor, but not the TNF receptor p75 or CD95. TNF-α (25 ng/ml) increased apoptosis in ECL cells approximately 4-fold, IFN-γ had no effect. Western blot analysis revealed that TNF-α caused degradation of IĸBα within 10 min. EMSA demonstrated that TNF-α led to increased DNA-binding activity of NFĸB and that proteasome inhibitors counteracted NFĸB activation. Proteasome inhibitors, specific antisense oligodeoxynucleotides against the p65 subunit of the NFĸB complex and the NO synthase inhibitor N^G-monomethyl-L-arginine completely prevented TNF-α-induced apoptosis. Our data suggest that TNF-α induces apoptosis of isolated gastric ECL cells via activation of NFĸB and the generation of NO.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor Necrosis Factor-Alpha Effects on Rat Gastric Enterochromaffin-Like Cells

Huber

Zanner²,

Pohlinger³

et al. 2002

Digestion

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“…The release of these cytokines in turn induces the accumulation of inflammatory cells and also leads to a sustained functional impairment of mucosal cells. For example, incubation of parietal cells (PC) and enterochromaffin-like cells with IL-1␤ induced apoptosis of these cells that are crucial for acid secretion (9,12,18,25,26).…”

mentioning

confidence: 99%

Helicobacter pyloriinduces apoptosis of rat gastric parietal cells

Neu¹,

Randlkofer²,

Neuhofer³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gastric Helicobacter pylori infection may lead to multifocal atrophic corpus gastritis associated with loss of epithelial cells as well as glandular structures. The current work investigated H. pylori effects on cell death of isolated, nontransformed rat parietal cells (PC). Highly enriched rat PC (>97%) were isolated from gastric mucosa and cultured in serum-free medium over 24 h. The cells were cocultured over 8 h with cytotoxin-associated immunodominant protein (cagA)+/vacuolating toxin (vacA)+ or with cagA−/vacA− H. pylori laboratory strains and also with H. pylori mutants deleted in several genes of the cag pathogenicity island. Staphylococcus aureus or Campylobacter jejuni were used as controls. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and electron microscopy. Interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant (CINC)-1 secretion was measured by ELISA. Activation of nuclear factor-κB (NF-κB) was studied in nuclear extracts of PC by electrophoretic mobility shift assay. Apoptosis of PC was induced in a concentration- and time-dependent manner by cagA+/vacA+ H. pylori strains but not by cagA−/vacA−negative strains or by the cagE knockout mutant. S. aureusand C. jejuni had no effect. PC showed no IL-8 or CINC-1 secretion on exposure to cagA+/vacA+ H. pylori. cagA+/vacA+ strains induced activation of NF-κB complexes in nuclear extracts of PC, which were composed of p65 and p50 subunits. No significant stimulation of NF-κB activation was detected by incubation of PC with the cagE knockout mutant. Preincubation of PC with antisense but not missense oligodeoxynucleotides against the p65 subunit significantly reduced DNA binding to the κB recognition sequence. The p65 oligonucleotides as well as the proteasome inhibitor N-CBZ-isoleucin-glutamin-(o-t-butyl-)-alanin-leucin and the nitric oxide synthase inhibitor N G-monomethyl-l-arginine completely prevented PC apoptosis induced by cagA+/vacA+ strains. In summary, cagE presence appears to be essential for H. pylori-induced apoptosis of gastric parietal cells, and this effect is dependent on the activation of NF-κB and production of nitric oxide.

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Apoptosis in Exocrine Acinar Cells

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Apoptosis: Involvement of Oxidative Stress and Intracellular Ca2+ Homeostasi

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IL-1β–Induced apoptosis in rat gastric enterochromaffin-like cells is mediated by iNOS, NF-κB, and Bax protein

Cited by 42 publications

References 49 publications

Tumor Necrosis Factor-Alpha Effects on Rat Gastric Enterochromaffin-Like Cells

Tumor Necrosis Factor-Alpha Effects on Rat Gastric Enterochromaffin-Like Cells

Helicobacter pyloriinduces apoptosis of rat gastric parietal cells

Apoptosis in Exocrine Acinar Cells

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