RRC ID 1942
Author Luo JC, Shin VY, Yang YH, Wu WK, Ye YN, So WH, Chang FY, Cho CH.
Title Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation.
Journal Am. J. Physiol. Gastrointest. Liver Physiol.
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.
Volume 288(1)
Pages G32-8
Published 2005-1
DOI 10.1152/ajpgi.00093.2004
PII 00093.2004
PMID 15256360
MeSH Animals Apoptosis Arachidonic Acid / pharmacology Cell Proliferation* Cell Survival Cyclooxygenase 2 Dinoprostone / pharmacology Epithelial Cells / physiology Gastric Mucosa / cytology* Gastric Mucosa / pathology* Gene Expression Regulation Prostaglandin-Endoperoxide Synthases / biosynthesis Rats Stomach / cytology* Stomach / physiology Tumor Necrosis Factor-alpha / pharmacology*
IF 3.293
Times Cited 25
Human and Animal Cells RGM1