Antiangiogenic Effect of a Highly Selective Cyclooxygenase-2 Inhibitor on Gastric Ulcer Healing in Rats

2002 ◽  
Vol 183 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Jin Sheng Guo ◽  
Chi Hin Cho ◽  
Edgar Shiu Lam Liu ◽  
Hau Tim Choy ◽  
Ji Yao Wang ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Cyclooxygenase 2 ◽  
Antiangiogenic Effect ◽  
Gastric Ulcer Healing

Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors

2002 ◽  
Vol 442 (1-2) ◽  
pp. 125-135 ◽  
Author(s):  
Bettina Berenguer ◽  
Catalina Alarcón de la Lastra ◽  
Francisco Javier Moreno ◽  
Maria José Martı́n
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Cyclooxygenase 2 ◽  
Chronic Gastric Ulcer ◽  
Gastric Ulcer Healing ◽  
Cyclooxygenase 2 Inhibitors

Role of nuclear factor-κB in gastric ulcer healing in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1296-G1304 ◽  
Author(s):  
Satoru Takahashi ◽  
Takuya Fujita ◽  
Akira Yamamoto
Keyword(s):  
Gastric Ulcer ◽  
Mrna Expression ◽  
Ulcer Healing ◽  
Nuclear Factor Κb ◽  
Normal Mucosa ◽  
Cyclooxygenase 2 ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Gastric Ulcer Healing

We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE2 production were also reduced. These results demonstrate that NF-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.

Neutrophils delay gastric ulcer healing by inhibiting angiogenesis in rats: Involvement of antiangiogenic effect of tumor necrosis factor-α

2001 ◽  
Vol 120 (5) ◽  
pp. A148
Author(s):  
Toshio Watanabe ◽  
Kazuhide Higuchi ◽  
Masaki Hamaguchi ◽  
Kazunari Tominaga ◽  
Yasuhiro Fujiwara ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Tumor Necrosis Factor ◽  
Ulcer Healing ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Antiangiogenic Effect ◽  
Gastric Ulcer Healing ◽  
Factor Α ◽  
Necrosis Factor

Cyclooxygenase-2-regulated vascular endothelial growth factor release in gastric fibroblasts

2004 ◽  
Vol 287 (2) ◽  
pp. G444-G451 ◽  
Author(s):  
Shuhei Miura ◽  
Atsushi Tatsuguchi ◽  
Ken Wada ◽  
Hiroki Takeyama ◽  
Yoko Shinji ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Repair Process ◽  
Cyclooxygenase 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gastric Ulcer Healing ◽  
Cox 2 ◽  
Vegf Release

VEGF is a highly specific stimulator of endothelial cells and may play an important role in angiogenesis in the process of tissue regeneration. We previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of the ulcer bed is involved in the ulcer repair process. To clarify the role of COX-2 in angiogenesis during gastric ulcer healing, we investigated the relation between COX-2 expression and VEGF production in human gastric fibroblasts in vivo and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL-1α or IL-1β in the presence or absence of NS-398, a selective COX-2 inhibitor. Supernatant VEGF and PGE2 concentrations were measured by enzyme-linked immunosorbent assay. COX-2 expression in fibroblasts was determined by Western blot analysis. VEGF and COX-2 expression in surgical resections of human gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation. IL-1 also stimulated PGE2 production in gastric fibroblasts via COX-2 induction. NS-398 significantly suppressed VEGF and PGE2 release from IL-1-stimulated gastric fibroblasts; concurrent addition of PGE2 restored NS-398-inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in fibroblast-like cells in the ulcer bed of gastric tissues. These results suggest that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated by IL-1 in vitro and that angiogenesis induced by the COX-2-VEGF pathway might be involved in gastric ulcer healing.

Rebamipide Reduces Delay in Gastric Ulcer Healing in Cyclooxygenase-2-Deficient Mice

2005 ◽  
Vol 50 (S1) ◽  
pp. S63-S69 ◽  
Author(s):  
Toshio Watanabe ◽  
Kazuhide Higuchi ◽  
Koichi Taira ◽  
Eiji Sasaki ◽  
Masatsugu Shiba ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Cyclooxygenase 2 ◽  
Gastric Ulcer Healing ◽  
Deficient Mice

Role of cyclooxygenase-2 in modulating gastric acid secretion in the normal and inflamed rat stomach

2000 ◽  
Vol 279 (6) ◽  
pp. G1292-G1297 ◽  
Author(s):  
Kirsty Barnett ◽  
Cameron J. Bell ◽  
Webb McKnight ◽  
Michael Dicay ◽  
Keith A. Sharkey ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Ulcer Healing ◽  
Cyclooxygenase 2 ◽  
Gastric Ulcer Healing ◽  
Cyclooxygenase 1 ◽  
Basal Acid ◽  
Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs elevate gastric acid secretion, possibly contributing to their ability to interfere with gastric ulcer healing. Inhibitors of cyclooxygenase-2 have been shown to delay experimental gastric ulcer healing. In the present study, we tested the hypothesis that cyclooxygenase-2-derived prostaglandins modulate gastric acid secretion. Studies were performed in normal rats and in rats with iodoacetamide-induced gastritis. Inflammation in the latter group was confirmed histologically and by a threefold increase in tissue levels of the granulocyte marker myeloperoxidase and was also associated with overexpression of cyclooxygenase-2 in the stomach. Basal acid secretion in both groups of rats was not affected by pretreatment with DuP-697, a selective inhibitor of cyclooxygenase-2. A nonselective cyclooxygenase inhibitor, indomethacin, had no effect on acid secretion in normal rats but caused a doubling of acid secretion in the rats with gastritis. DuP-697 had no effect on pentagastrin-induced secretion in either group of rats. Gastritis itself was associated with significantly increased pentagastrin-induced acid secretion, and this was further increased in rats pretreated with indomethacin. These results suggest that in a setting of gastric inflammation, prostaglandins derived from cyclooxygenase-1, not cyclooxygenase-2, exert inhibitory effects on acid secretion.

Gastric ulcer healing is regulated by platelets through endostatin release: Modulation by ticlopidine, aspirin and celecoxib

2001 ◽  
Vol 120 (5) ◽  
pp. A143-A143
Author(s):  
L MA ◽  
S ELLIOTT ◽  
G CIRINO ◽  
A BURET ◽  
J WALLACE
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Gastric Ulcer Healing
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