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

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.

Annexin-1 modulates repair of gastric mucosal injury

2008 ◽  
Vol 294 (3) ◽  
pp. G764-G769 ◽  
Author(s):  
Gary R. Martin ◽  
Mauro Perretti ◽  
Roderick J. Flower ◽  
John L. Wallace
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Mucosal Injury ◽  
Formyl Peptide Receptor ◽  
Gastric Mucosal Damage ◽  
Gastric Ulcers ◽  
Wild Type ◽  
Gastric Ulcer Healing ◽  
Annexin 1 ◽  
Deficient Mice

Annexin-1 is a glucocorticoid-inducible protein that plays an important effector role in the resolution of inflammation and has recently been shown to contribute to the resistance of the stomach to injury. Using an integrated genetic and pharmacological approach, we have tested the hypothesis that annexin-1 contributes to the healing of mucosal injury, given that such injury is accompanied by an inflammatory response, which is often associated with an overexpression of annexin-1 expression. Gastric ulcers were induced in mice through serosal application of acetic acid. Annexin-1 expression during the healing of the ulcers was examined. The effects on gastric ulcer healing of treatment with an annexin-1 mimetic (Ac2-26), an antagonist of the annexin-1 receptor (Boc2), or a glucocorticoid (dexamethasone) were examined. Finally, susceptibility to and healing of indomethacin-induced gastric lesions were compared in wild-type and annexin-1-deficient mice. Expression of annexin-1 was significantly increased in the gastric ulcer margin throughout the healing process. Treatment with an annexin-1 mimetic (Ac2-26) significantly enhanced gastric ulcer healing. In contrast, both dexamethasone and an formyl peptide receptor-like-1 (FPRL-1) antagonist impaired the early phase of ulcer healing. Annexin-1-deficient mice exhibited the same susceptibility as wild-type mice to indomethacin-induced gastric damage, but the healing of that damage was impaired in the former. These data support the hypothesis that annexin-1 contributes significantly to the process of healing of gastric mucosal damage.

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.

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

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

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

2001 ◽  
Vol 120 (5) ◽  
pp. A143
Author(s):  
Li Ma ◽  
Susan N. Elliott ◽  
Giuseppe Cirino ◽  
Andre Buret ◽  
John L. Wallace
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Gastric Ulcer Healing
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