Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue

Lab Invest. 2005 Feb;85(2):225-36. doi: 10.1038/labinvest.3700200.


Recently, three different prostaglandin E2 synthases have been identified: microsomal prostaglandin E synthase (mPGES)-1, cytosolic PGES (cPGES), and mPGES-2; however, their role and connection to cyclooxygenase (COX)-2 in the gastric ulcer repair process remain unknown. Therefore, we examined mPGES-1, cPGES, and mPGES-2 expression and localization in the stomach in vitro and in vivo. Tissues were obtained from Helicobacter pylori (H. pylori)-infected patients and consisted of surgical resections of gastric ulcers, or biopsies of gastric ulcers or gastritis. mPGES-1 mRNA and protein expression levels were examined by real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. mPGES-1, cPGES, and mPGES-2 localization were analyzed immunohistochemically. Induction of PGES expression in response to interleukin (IL)-1beta was examined in vitro in the cultured human gastric fibroblast line Hs262.St. Real-time PCR analysis of mPGES-1 mRNA expression in biopsy samples showed significantly higher expression levels in open than in closed gastric ulcer tissue. Western blot analysis showed mPGES-1 protein expression limited to open ulcer tissue, while mPGES-2 and cPGES immunoreactivities were seen in both open and closed ulcer tissue. Immunohistochemical analysis showed strong mPGES-1 expression in fibroblasts and macrophages of the ulcer bed, paralleling COX-2 expression. cPGES and mPGES-2 expression levels were seen in both fibroblasts of the ulcer bed and in epithelial cells. Furthermore, stronger cPGES and mPGES-2 immunoreactivities were seen in scattered mast cell-like cells and neuroendocrine-like cells, respectively. Induction of mPGES-1 expression in response to IL-1beta was seen in cultured gastric fibroblasts in vitro, and double immunostaining showed mPGES-1 coexpression with COX-2 in fibroblasts of the ulcer bed in vivo. In conclusion, mPGES-1, cPGES, and mPGES-2 are all expressed in gastric ulcer tissue, but only mPGES-1 parallels COX-2 expression in mesenchymal and inflammatory cells of the ulcer bed, suggesting a key role for this enzyme in the ulcer repair process.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Cell Line
  • Cyclooxygenase 2
  • Cytosol / enzymology
  • Enzyme Induction / drug effects
  • Female
  • Fibroblasts / enzymology
  • Gastritis / enzymology*
  • Gastritis / microbiology
  • Helicobacter Infections / enzymology
  • Helicobacter pylori / enzymology
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology
  • Intramolecular Oxidoreductases / metabolism*
  • Isoenzymes / metabolism*
  • Macrophages / metabolism
  • Male
  • Membrane Proteins
  • Microsomes / enzymology*
  • Middle Aged
  • Polymerase Chain Reaction
  • Prostaglandin-E Synthases
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / metabolism
  • Stomach Ulcer / enzymology*
  • Stomach Ulcer / microbiology
  • Stomach Ulcer / surgery


  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • PTGES2 protein, human
  • Prostaglandin-E Synthases