Dexamethasone inhibits tumor necrosis factor-alpha-stimulated gastric epithelial cell migration

J Chin Med Assoc. 2009 Oct;72(10):509-14. doi: 10.1016/S1726-4901(09)70419-8.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dexamethasone / pharmacology*
  • Dinoprostone / analysis
  • Fibroblast Growth Factor 2 / analysis
  • Gastric Mucosa / chemistry
  • Gastric Mucosa / cytology
  • Gastric Mucosa / drug effects*
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Dexamethasone
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone