Summary
Background: CXC chemokines such as interleukin (IL)‐8 are neutrophil chemoattractants, the levels of which increase in Helicobacter pylori‐infected gastric mucosa. Many investigators have focused on the chemotactic aspects of IL‐8; however, CXC chemokines are also reported to have angiogenic activity and to serve as remodelling factors. Rat GRO/CINC‐1 is a rodent counterpart of human GROα, a member of the family of CXC chemokines. Gastric mucosa infected with H. pylori is in a state of hyperproliferation, with increases in the amounts of growth factors such as hepatocyte growth factor (HGF).
Aim: To investigate whether rat GRO/CINC‐1 had growth‐stimulating activity for gastric epithelial cells.
Methods: The rat gastric epithelial cell line RGM‐1 was incubated in serum‐free medium for 12 h to adjust the cell cycle to the G0 phase, and GRO/CINC‐1 was then added for 24 h. The total cell number was determined by fluorogenic analysis after propidium iodide staining, and cell proliferation was assessed by measuring 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation. The activity of p42/p44 mitogen‐activated protein kinase (MAPK) was measured 5–20 min after the start of GRO/CINC‐1 exposure.
Results: Cultures treated with GRO/CINC‐1 showed a significant increase in cell number and BrdU incorporation in a concentration‐dependent fashion. The MAPK activity increased within 5 min after GRO/CINC‐1 application and returned to the control level at 20 min.
Conclusion: The growth‐stimulatory effect of GRO/CINC‐1 on rat gastric epithelial cells suggests a dual function of this chemokine: proinflammatory action and induction of epithelial proliferation.
Background:
Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis.
Aim:
To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction.
Methods:
Forty‐six H. pylori‐infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme‐linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks.
Results:
In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus.
Conclusions:
Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density.
Aim:
To examine whether proton pump inhibitors modify the production of oxygen‐derived free radicals and related cytokines in the human gastric mucosa infected with H. pylori.
Methods:
Thirty‐four H. pylori‐positive peptic ulcer patients (23 gastric ulcer, 11 duodenal ulcer) were enrolled. Biopsy tissue samples were obtained endoscopically from the antrum and corpus. Tissue content of neutrophil myeloperoxidase (myeloperoxidase) and IL‐8 was measured by ELISA. Mucosal production of oxygen‐derived free radical was measured using luminol‐dependent chemiluminescence (ChL). A proton pump inhibitor (either lansoprazole 30 mg, omeprazole 20 mg, or rabeprazole 10 mg) was administered daily by mouth to all patients for 8 weeks. Endoscopic examination was then repeated, and biochemical analysis was performed.
Results:
Antral myeloperoxidase decreased significantly after proton pump inhibitor treatment (5.23 ± 7.00–2.76 ± 5.11 ng/mg, P < 0.02), but corpus myeloperoxidase was unchanged. IL‐8 was also modified by proton pump inhibitors and these changes were parallel to those of myeloperoxidase. Corpus ChL was significantly increased from 88.5 ± 69.8–159 ± 172 counts/10 s/mg after proton pump inhibitor treatment, whereas antrum ChL was not altered. H. pylori infection rate was decreased in the antrum as well as the corpus.
Conclusions:
Proton pump inhibitor treatment stimulated oxygen‐derived free radical production in the corpus mucosa.
Administration of RPZ not only inhibited gastric H. pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH.
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