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Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa
  1. L M Jacksona,
  2. K C Wu,a,
  3. Y R Mahidaa,
  4. D Jenkinsb,
  5. C J Hawkeya
  1. aDivision of Gastroenterology, University Hospital, Nottingham, UK, bDivision of Pathology, University Hospital, Nottingham, UK
  1. Professor C J Hawkey, Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK. cj.hawkey{at}nottingham.ac.uk

Abstract

BACKGROUND AND AIMS Constitutive cyclooxygenase (COX) 1 is believed to mediate prostaglandin dependent gastric protection. However, gastric mucosa contains cells capable of expressing inducible COX-2. We therefore investigated COX-1 and COX-2 expression, localisation, and activity in normal and abnormal human gastric mucosa.

METHODS COX-1 and COX-2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis, and their contribution to prostaglandin (PG)E2 synthesis using selective enzyme inhibitors.

RESULTS There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivity in some sections. Immunostaining was specifically abolished by antigen absorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 and COX-2 immunostaining was increased inHelicobacter pylori gastritis, particularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE2 synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucosa; p=0.017) which was significantly inhibited by COX-1 but not COX-2 inhibition. Increased COX-2 immunostaining in macrophages, endothelial cells, and myofibroblasts (with reduced epithelial expression) was seen at the rim of ulcers.

CONCLUSION COX-2, as well as COX-1, is expressed by normal human gastric mucosa and is increased at the rim of ulcers. Although both are increased withH pylori, COX-1 contributes more than COX-2 to gastric PGE2 production.

  • stomach
  • gastric mucosa
  • cyclooxygenases
  • Helicobacter pylori
  • ulceration
  • prostaglandins

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