Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans

Abstract

Background-Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. Aims-To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. Patients and methods-Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n=9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n=45) and H pylori negative healthy subjects (n=15). COX expression was detected by semiquantitative reverse transcriptionpolymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. Results-COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. Conclusions-Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process. (Gut 2000;46:782-789)

Cutting Edge: Cyclooxygenase-2 Activation Suppresses Th1 Polarization in Response toHelicobacter pylori

“…We and others have shown that H. pylori increases COX-2 expression in human gastric mucosa (14,15) and in gastric epithelial cell lines (21,25). H. pylori is strongly linked to gastric cancer (26), and the chronic inflammation associated with the longstanding infection is presumed to be the main cause.…”

“…We and others have demonstrated that the inducible form of cyclooxygenase, (COX) 4 -2, is up-regulated in human H. pylori gastritis tissues and localizes to lamina propria mononuclear cells (14,15). Increased levels of PGE 2 have also been demonstrated in the infected gastric mucosa (16).…”

High Cyclooxygenase-2 Expression Following Neoadjuvant Radiochemotherapy Is Associated with Minor Histopathologic Response and Poor Prognosis in Esophageal Cancer

“…On the other hand, COX-2 is an inducible gene, originally found to be up-regulated by inflammation or other stimuli such as mitogens, cytokines, various growth factors, and tumor promoters (10 -12). COX-2 was shown to be activated in inflammatory cells, vascular endothelial cells, and fibroblasts (13), as well as macrophages (14). High levels of COX-2 have also been reported in a variety of cancer types, including esophageal carcinoma (15).…”

Induction of Cyclo-oxygenase-2 Expression in Naturally Occurring Gastric Ulcers

“…In the normal stomach of humans and animals, most studies found COX-2 mRNA and protein to be expressed at low or undetectable levels, and the physiological role of COX-2 in normal stomach remains to be defined (Kargman et al 1996;Ristimaki et al 1997;Zimmermann et al 1998;Jackson et al 2000;Sung et al 2000). However, COX-2 overexpression has been reported in several different pathological gastric conditions, including ulcer healing (Mizuno et al 1997;Ristimaki et al 1997;Kishimoto et al 1998;Sawaoka et al 1998;Shigeta et al 1998;Fu et al 1999;McCarthy et al 1999;Jackson et al 2000;Sung et al 2000;Tatsuguchi et al 2000). In the latter, induced COX-2 expression was detected at the ulcer margins or in the ulcer bed by immunohistochemistry in gastric ulcers in humans and in experimentally induced gastric ulcers in rats and mice (Mizuno et al 1997;Shigeta et al 1998;Jackson et al 2000;Tatsuguchi et al 2000).…”