Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation.
TNF-alpha is a cytokine produced during gastric mucosal injury. We examined whether TNF-alpha 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-alpha treatment (1-10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-alpha treatment significantly increased cytosolic phospholipase A(2) and cyclooxygenase-2 (COX-2) protein expression and PGE(2) 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-alpha on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE(2) 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-alpha on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE(2) significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-alpha plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-alpha receptor and activation of the arachidonic acid/PG pathway.
Luo
Jiing Chyuan
JC
Division of Gastroenterology, Deprtment of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taiwan.
Shin
Vivian Yvonne
VY
Yang
Ying Hua
YH
Wu
William Ka Kei
WK
Ye
Yi Ni
YN
So
Wallace Hau Leung
WH
Chang
Full Young
FY
Cho
Chi Hin
CH
D000818:Animals; D017209:Apoptosis; D016718:Arachidonic Acid / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D005753:Gastric Mucosa / Q000166:cytology* / Q000473:pathology*; D005786:Gene Expression Regulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D013270:Stomach / Q000166:cytology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone