Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats

Am J Physiol. 1998 Nov;275(5):G1137-45. doi: 10.1152/ajpgi.1998.275.5.G1137.


It has been reported that cyclooxygenase-2 (COX-2) may play a crucial role in gastric ulcer healing. We examined the localization of COX-2 and the regulation of COX-2 mRNA expression in acetic acid ulcers in rats. PGE2 production was elevated in ulcerated tissue but not in intact tissue. COX-2 mRNA expression was induced in only the ulcerated tissue, and COX-2 protein was found in fibroblasts, monocytes/macrophages, and granulocytes. A selective COX-2 inhibitor inhibited increased PGE2 production by the ulcerated tissue. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) mRNAs were also expressed only in the ulcerated tissue. In a culture of isolated ulcer base, blockade of IL-1beta and TNF-alpha reduced COX-2 mRNA expression and PGE2 production. In contrast, COX-2 mRNA expression and PGE2 production were promoted by prevention of TGF-beta1 action. These results indicate that COX-2 protein is highly localized in the base of gastric ulcers in rats and that COX-2 mRNA expression might be regulated positively by IL-1beta and TNF-alpha and negatively by TGF-beta1.

MeSH terms

  • Acetic Acid
  • Animals
  • Antibodies / pharmacology
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / metabolism
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-1 / physiology
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism*
  • Male
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / biosynthesis
  • Rats
  • Reference Values
  • Stomach Ulcer / enzymology
  • Stomach Ulcer / metabolism*
  • Stomach Ulcer / pathology
  • Time Factors
  • Transcription, Genetic* / drug effects
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / physiology
  • Wound Healing / physiology


  • Antibodies
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Isoenzymes
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Acetic Acid