Gut 2000;47:762-770 ( December )

Article

Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa L M Jackson^a, K C Wu ^a, Y R Mahida^a, D Jenkins^b, C J Hawkey^a

^a Division of Gastroenterology, University Hospital, Nottingham, UK, ^b Division of Pathology, University Hospital, Nottingham, UK

Correspondence to: Professor C J Hawkey, Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK. cj.hawkey{at}nottingham.ac.uk

Accepted for publication 11 January 2000

BACKGROUND AND AIMSConstitutive 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.
METHODSCOX-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.
RESULTSThere 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 in Helicobacter 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.
CONCLUSIONCOX-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 with H pylori, COX-1 contributes more than COX-2 to gastric PGE₂ production.


Keywords: stomach; gastric mucosa; cyclooxygenases; Helicobacter pylori; ulceration; prostaglandins

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Present address: Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China

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© 2000 by Gut
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