Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa

Background and aims-Constitutive cyclooxygenase (COX) 1 is believed to medi ate prostaglandin dependent gastric protection. However, gastric mucosa con tains cells capable of expressing inducible COX-2. We therefore investigate d COX-1 and COX-2 expression, localisation, and activity in normal and abno rmal 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 c ontribution to prostaglandin (PG)E-2 synthesis using selective enzyme inhib itors. Results-There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivi ty in some sections. Immunostaining was specifically abolished by antigen a bsorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 an d COX-2 immunostaining was increased in Helicobacter pylori gastritis, part icularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE(2) synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucose; 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 epithe lial expression) was seen at the rim of ulcers. Conclusion-COX-2, as well as COX-1, is expressed by normal human gastric mu cosa and is increased at the rim of ulcers. Although both are increased wit h H pylori, COX-1 contributes more than COX-2 to gastric PGE(2) production.