Role of cyclooxygenase-2 in gastric mucosal defense

“…The early phase is characterized by rapid epithelial cell migration in the absence of proliferation, whereas the late phase involves cell division and cell proliferation to fill in the defect and restore mucosal architecture (23,27,32). Cytokines and growth factors can stimulate cyclooxygenase-2 (COX-2) expression in different tissues, and increased COX-2 expression has been demonstrated to be important in gastric mucosal defense and ulcer healing (2,4,13,17,26). TNF-␣ has been reported to indirectly stimulate cell migration through the increased production of hepatocyte growth factor and interleukin-8 (24,32).…”

mentioning

confidence: 99%

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

Luo

Shin

Yang

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

is a cytokine produced during gastric mucosal injury. We examined whether TNF-␣ could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-␣ treatment (1-10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-␣ treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-␣ on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5 H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-␣ on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-␣ plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-␣ receptor and activation of the arachidonic acid/PG pathway. cyclooxygenase; dexamethasone; phospholipase A2; prostaglandin E2

show abstract

“…It is expressed in the stomach and plays diverse roles in cases of mucosal injury by inducing prostaglandins in the stomach (14). COX-2 also plays an important role in the development of various kinds of cancer (15-18); indeed, the correlation between enhanced expression of COX-2 and gastric cancer has been previously reported (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

Shibata

Arisawa

Tahara³

et al. 2008

Mol Med Report

View full text Add to dashboard Cite

Abstract.A polymorphism within the 3'-UTR 8473T¨C of the cyclooxygenase-2 (COX-2) gene, which plays a role in gastrointestinal cancer development, has been associated with susceptibility to malignant disease. Here, we report on the interaction between the COX-2 3'-UTR T¨C polymorphism and gastric cancer development. DNA from 121 Japanese patients with gastric cancer and 126 age-matched control patients was examined for the COX-2 polymorphism by PCR-RFLP. Odds ratios and the 95% confidence interval (CI) were calculated. Homozygous carriage of the COX-2 8473C allele tended to be associated with an increased risk of gastric cancer compared to the T allele homozygotes of the subjects (OR=3.70; 95% CI, 0.96-14.25). The CC allele was associated with a significant increased risk of diffuse-type gastric cancer (OR=5.29; 95% CI, 1.18-23.70). These findings suggest that the COX-2 3'-UTR 8473T¨C polymorphism could be used as a marker for genetic susceptibility to gastric cancer in Japanese populations.

show abstract

Role of cyclooxygenase-2 in gastric mucosal defense

Cited by 77 publications

References 0 publications

Celecoxib Treatment Alters the Gene Expression Profile of Normal Colonic Mucosa

Celecoxib Treatment Alters the Gene Expression Profile of Normal Colonic Mucosa

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

Contact Info

Product

Resources

About