Journal of the Chinese Medical Association
Volume 72, Issue 10 , Pages 509-514, October 2009

Dexamethasone Inhibits Tumor Necrosis Factor-α-stimulated Gastric Epithelial Cell Migration

  • Jiing-Chyuan Luo

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr Jiing-Chyuan Luo, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
    • ,
  • Chi-Hin Cho

      Affiliations

    • Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
    • ,
  • Ka-Man Ng

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Kuo-Wei Hsiang

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Ching-Liang Lu

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Tseng-Shing Chen

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Full-Young Chang

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Han-Chieh Lin

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Chin-Lin Perng

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Shou-Dong Lee

      Affiliations

    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.

Received 20 May 2009; accepted 7 September 2009.

Article Outline

Background

Cell migration (restitution) occurs in the early phase of gastric ulcer healing. Tumor necrosis factor (TNF)-αis 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-α-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-α treatment (10 ng/mL) for 12–48 hours significantly increased RGM-1 cell migration, and TNF-α 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-α 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-α plays a regulatory role in rat gastric epithelial cell migration and dexamethasone inhibited TNF-α-stimulated cell migration, which was associated with a decrease in COX-2 expression and PGE2 formation. [J Chin Med Assoc 2009;72(10):509–514]

Key Words:  cell migration (restitution) , cyclooxygenase-2 , dexamethasone , gastric ulcer healing , tumor necrosis factor-α

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Luo JC, Shin VY, Liu ESL, So WHL, Ye YN, Chang FY, et al. Non-ulcerogenic dose of dexamethasone delays gastric ulcer healing in rats . J Pharmacol Exp Ther . 2003;307:692–698
  2. Yoo J , Lotz MM , Matthews JB . Cytokines in restitution . In:  Cho CH ,  Wang JY editor. Gastrointestinal Mucosal Repair and Experimental Therapeutics . 1st edition. Basel: Karger; 2002;p. 14–28
  3. Silen W , Ito S . Mechanisms for rapid re-epithelialization of gastric mucosal surface . Annu Rev Physiol . 1985;47:217–229
  4. Luo JC, Shin VY, Liu ESL, Ye YN, Wu WKK, So WHL, et al  Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs . Eur J Pharmacol . 2004;485:275–281
  5. Szabo S , Khomenko T , Gombos Z , Deng XM , Jadus MR , Yoshida M . Review article: transcription factors and growth factors in ulcer healing . Aliment Pharmacol Ther . 2000;14(Suppl):33–43
  6. Tarnawski A , Szabo IL , Husain SS , Soreghan B . Regeneration of gastric mucosa during ulcer healing is triggered by growth factors and signal transduction pathways . J Physio Paris . 2001;95:337–344
  7. Tarnawski AS . Cellular and molecular mechanisms of gastrointestinal ulcer healing . Dig Dis Sci . 2005;50(Suppl):S24–S33
  8. Basson MD , Modlin IM , Madri JA . Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor . J Clin Invest . 1992;90:15–23
  9. Martin P . Wound healing—;aiming for perfect skin regeneration . Science . 1997;276:75–81
  10. Pai R , Szabo IL , Giap AQ , Kawanaka H , Tarnawski AS . Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signal . Life Sci . 2001;69:3055–3071
  11. Takahashi S , Shigeta JI , Inoue H , Tanabe T , Okabe S . Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats . Am J Physiol Gastrointest Liver Physiol . 1998;275:G1137–G1145
  12. Takahashi M, Ota S, Hata Y, Mikami Y, Azuma N, Nakamura T, et al  Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach . J Clin Invest . 1996;98:2604–2611
  13. Luo JC, Shin VY, Yang YH, Wu WKK, Ye YN, So WHL, et al  Tumor necrosis factor-α stimulates gastric epithelial cell proliferation . Am J Physiol Gastrointest Liver Physiol . 2005;288:G32–G38
  14. Kobayashi I, Kawano S, Tsuji S, Matsui H, Nakama A, Sawaoka H, et al  RGM1, a cell line derived from normal gastric mucosa of rat . In Vitro Cell Dev Biol Animal . 1996;32:259–261
  15. Luo JC, Lin HY, Lu CL, Wang LY, Chang FY, Lin HC, et al  Dexamethasone inhibits basic fibroblast growth factor-stimulated gastric epithelial cell proliferation . Biochem Pharmacol . 2008;76:841–849
  16. Shin VY , Liu ESL , Koo MWL , Luo JC , So WHL , Cho CH . Nicotine suppresses gastric wound repair via the inhibition of polyamine and K+ channel expression . Eur J Pharmacol . 2002;444:115–121
  17. Netzer P, Halter F, Ma TY, Hoa N, Nguyen N, Nakamura T, et al. Interactions of hepatocyte growth factor and non-steroidal anti-inflammatory frogs during gastric epithelial wound healing . Digestion . 2003;67:118–128
  18. Ng KM, Cho CH, Chang FY, Luo JC, Lin HC, Lin HY, et al  Omeprazole promotes gastric epithelial cell migration . J Pharm Pharmacol . 2008;60:655–660
  19. Horie-Sakata K , Shimada T , Hiraishi H , Terano A . Role of cyclooxygenase-2 in hepatocyte growth factor-mediated gastric epithelial restitution . J Clin Gastroenterol . 1998;27(Suppl):S40–S60
  20. Loew D , Schuster O , Graul EH . Dose-dependent pharmacokinetics of dexamethasone . Eur J Clin Pharmacol . 1986;30:225–230
  21. Czock D , Keller F , Rasche FM , Haussler U . Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids . Clin Pharmacokinet . 2005;44:61–98
  22. Luo JC, Chi CW, Lin HY, Chang FY, Lu CL, Chen CY, et al. Dexamethasone inhibits epidermal growth factor-stimulated gastric epithelial cell proliferation . J Pharmacol Exp Ther . 2007;320:687–694

PII: S1726-4901(09)70419-8

doi:10.1016/S1726-4901(09)70419-8

Journal of the Chinese Medical Association
Volume 72, Issue 10 , Pages 509-514, October 2009

Article Tools