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

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.

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Aqueous Extract of Enantia chlorantha (Annonaceae) Prevents the Delay in Chronic Gastric Ulcer Healing Caused by Indomethacin in Rats

British Journal of Pharmaceutical Research ◽

10.9734/bjpr/2015/19035 ◽

2015 ◽

Vol 8 (1) ◽

pp. 1-13

Author(s):

Kuissu Mesmine ◽

Enow-Orock George ◽

Mezui Christophe ◽

Nkwengoua Ernestine ◽

Tan Paul ◽

...

Keyword(s):

Gastric Ulcer ◽

Aqueous Extract ◽

Ulcer Healing ◽

Chronic Gastric Ulcer ◽

Gastric Ulcer Healing

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Effects of selective and non-selective COX-1 and COX-2 inhibitors on chronic gastric ulcer healing

Gastroenterology ◽

10.1016/s0016-5085(08)82974-5 ◽

2001 ◽

Vol 120 (5) ◽

pp. A598

Author(s):

Catalina Alarcon de La Lastra ◽

Bettina Berenguer ◽

Virginia Motilva ◽

Carmen La Casa ◽

Juan Manuel Herrerias ◽

...

Keyword(s):

Gastric Ulcer ◽

Ulcer Healing ◽

Chronic Gastric Ulcer ◽

Gastric Ulcer Healing ◽

Cox 2 ◽

Cox 2 Inhibitors ◽

Cox 1

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00537.2003 ◽

2004 ◽

Vol 287 (2) ◽

pp. G444-G451 ◽

Cited By ~ 39

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.

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