title: Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Deprtment of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taiwan.
authors.forename: Jiing Chyuan
authors.initials: JC
authors.lastname: Luo
authors.forename: Vivian Yvonne
authors.initials: VY
authors.lastname: Shin
authors.forename: Ying Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
authors.forename: Yi Ni
authors.initials: YN
authors.lastname: Ye
authors.forename: Wallace Hau Leung
authors.initials: WH
authors.lastname: So
authors.forename: Full Young
authors.initials: FY
authors.lastname: Chang
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
mesh_terms: 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*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone