Dexamethasone inhibits tumor necrosis factor-alpha-stimulated gastric epithelial cell migration.
BACKGROUND
Cell migration (restitution) occurs in the early phase of gastric ulcer healing. Tumor necrosis factor (TNF)-alpha is overexpressed at the ulcer margin and plays a physiologic role in gastric ulcer healing. Dexamethasone, which is a potent corticosteroid, delays rat gastric ulcer healing. We evaluated whether dexamethasone inhibited TNF-alpha-stimulated gastric epithelial cell migration using a rat normal gastric epithelial cell line (RGM-1).


METHODS
An artificial wound model was employed to measure cell migration. Western blot was performed to evaluate the possible mechanisms. Intracellular prostaglandin E2 level was measured using an enzyme-linked immunosorbent assay.


RESULTS
TNF-alpha treatment (10 ng/mL) for 12-48 hours significantly increased RGM-1 cell migration, and TNF-alpha treatment increased cyclooxygenase (COX)-2 protein expression 8 hours later and prostaglandin E2 (PGE2) synthesis 12 hours later compared with control (p < 0.05). Dexamethasone (10(-6) M) significantly inhibited the stimulatory effect of TNF-alpha on RGM-1 cell migration, which was associated with a significant decrease in COX-2 expression and PGE2 level in cells (p < 0.05).


CONCLUSIONS
TNF-alpha plays a regulatory role in rat gastric epithelial cell migration and dexamethasone inhibited TNF-alpha-stimulated cell migration, which was associated with a decrease in COX-2 expression and PGE2 formation.
Luo
Jiing-Chyuan
JC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. jcluo@vghtpe.gov.tw
Cho
Chi-Hin
CH
Ng
Ka-Man
KM
Hsiang
Kuo-Wei
KW
Lu
Ching-Liang
CL
Chen
Tseng-Shing
TS
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Perng
Chin-Lin
CL
Lee
Shou-Dong
SD
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone