Jackson L M, Wu K C, Mahida Y R, Jenkins D, Hawkey C J
Division of Gastroenterology, University Hospital, Nottingham, UK.
Gut. 2000 Dec;47(6):762-70. doi: 10.1136/gut.47.6.762.
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.
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)E(2) synthesis using selective enzyme inhibitors.
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 in Helicobacter pylori gastritis, particularly 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 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.
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 with H pylori, COX-1 contributes more than COX-2 to gastric PGE(2) production.
组成型环氧化酶（COX）-1被认为介导前列腺素依赖性胃保护作用。然而，胃黏膜含有能够表达诱导型COX-2的细胞。因此，我们研究了COX-1和COX-2在正常和异常人胃黏膜中的表达、定位及活性。
通过光镜和电镜免疫组织化学以及蛋白质印迹分析研究COX-1和COX-2的分布，并使用选择性酶抑制剂研究它们对前列腺素（PG）E2合成的作用。
在所有切片和分离细胞中均有强烈的壁细胞COX-1和COX-2免疫反应性，在一些切片中有巨噬细胞和成肌纤维细胞反应性。免疫染色通过抗原吸收被特异性消除。蛋白质印迹分析证实了COX-1和COX-2的表达。在幽门螺杆菌胃炎中，尤其是在胃腺中区和固有层炎症细胞中，COX-1和COX-2免疫染色增加。这与体外PGE2合成增加相关（62.4（13.5）pg/mg，未发炎黏膜中为36.3（15.5）pg/mg；p = 0.017），COX-1抑制可显著抑制该合成，但COX-2抑制无此作用。在溃疡边缘可见巨噬细胞、内皮细胞和成肌纤维细胞中COX-2免疫染色增加（上皮表达减少）。
正常人胃黏膜表达COX-2以及COX-1，且在溃疡边缘增加。虽然二者在幽门螺杆菌感染时均增加，但COX-1对胃PGE2产生的贡献大于COX-2。
