COX-1 and COX-2 conversely promote and suppress ischemia-reperfusion gastric injury in mice.

OBJECTIVE: Neutrophil activation followed by free radical production is a feature that is common to the various forms of gastric injury. However, the roles of cyclooxygenase (COX)-1 and -2 in neutrophil activation have yet to be clarified in the gastric mucosa. We examined the roles of both COX-1 and COX-2 in neutrophil activation and free radical production in ischemia-reperfusion (IR) injury in the gastric mucosa of mice. MATERIAL AND METHODS: Ischemia was induced by clamping the celiac artery for 30 min, then removing the clamp for 90 min. SC-560, a selective COX-1 inhibitor; NS-398, a selective COX-2 inhibitor; or rebamipide, a mucoprotective agent, was administered to mice 60 min before ischemia. Gastric damage was evaluated histologically and by measuring myeloperoxidase (MPO) activity. Expressions of COX protein and intercellular adhesion molecule (ICAM)-1 were evaluated by Western blot analysis and ELISA, respectively. Effects of these drugs on thiobarbituric acid reactive substances (TBARS) and gastric blood flow were also evaluated. RESULTS: COX-2 expression was induced in gastric mucosa 60 min after reperfusion, whereas COX-1 expression remained unaltered. Localization of COX-1 and ICAM-1 in IR-injured mucosa was observed mainly in endothelial cells, while COX-2 expression was detected in mesenchymal cells such as mononuclear cells, spindle-like cells and endothelial cells. SC-560 significantly decreased gastric blood flow at the reperfusion point and reduced gastric mucosal injury in IR mice. Furthermore, SC-560 pretreatment significantly reduced MPO activity, TBARS levels and ICAM-1 expression. In contrast, NS-398 significantly increased ICAM-1 expression, MPO activity and TBARS levels, and aggravated gastric damage in IR mice. Rebamipide pretreatment reduced both COX-2 expression and IR injury. CONCLUSIONS: In IR mice, COX-2 protects the gastric mucosa by down-regulating ICAM-1 expression, whereas COX-1 is involved in up-regulating reperfusion flow, thereby aggravating the mucosa.

ErbB2 without erbB3 expression in metaplastic columnar epithelium of Barrett's esophagus.

BACKGROUND/AIMS: ErbB2 expression in esophageal adenocarcinoma has been shown to correlate with its clinicopathological features. However, expression levels for EGF receptor, erbB2 and erbB3 in specialized columnar epithelium (SCE) of Barrett's esophagus have yet to be determined. To investigate the relationship between EGF family receptors and Barrett's esophagus, we examined expression levels for EGF receptor, erbB2 and erbB3 in SCE of Barrett's esophagus. METHODS: 10 consecutive patients with short- and long-segment Barrett's esophagus, and 10 control subjects without organic esophago-gastric diseases were enrolled. Biopsy samples of Barrett's mucosa stained or not stained with methylene blue applied endoscopically were used for histological evaluation and Western blot analysis of EGF receptor, erbB2 and erbB3 proteins. RESULTS: Mean length of Barrett's esophagus was 2.6 cm (range 1-8 cm) and all tissue samples from methylene blue stained Barrett's mucosa consisted of non-dysplastic SCE. In the Barrett's group, Western blot analysis showed that EGF receptor and erbB2 were equally and strongly expressed in SCE and squamous epithelium; in contrast, erbB3 expression in SCE was considerably weaker. In control subjects, all proteins showed strong expression for all samples. Immunohistochemical analysis of SCE in Barrett's esophagus showed positive EGF receptor and erbB2 expression, and no erbB3 expression. CONCLUSIONS: ErbB2 is strongly expressed in both non-dysplastic SCE and squamous epithelium, whereas erbB3 expression is essentially limited to the squamous epithelium. .

Teprenone, but not H2-receptor blocker or sucralfate, suppresses corpus Helicobacter pylori colonization and gastritis in humans: teprenone inhibition of H. pylori-induced interleukin-8 in MKN28 gastric epithelial cell lines.

BACKGROUND: The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells. MATERIALS AND METHODS: A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23, p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24, p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylori-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner. CONCLUSIONS: Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.