Katori M, Majima M
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Inflamm Res. 2000 Aug;49(8):367-92. doi: 10.1007/s000110050605.
In addition to housekeeping cyclooxygenase (COX)-1, which is constitutively expressed in many body cells, an inducible COX-2 has been described and cloned. Induction or presence of COX-2 has been reported not only in isolated cells, but also in cells in various tissues, as well as in both physiological and pathophysiological states, including acute exudative inflammation, proliferative inflammation, animal arthritis, rheumatoid arthritis, angiogenesis, bone absorption, gastric ulcer, colon cancer, hyperalgesia, Alzheimer's disease and certain states of the kidney, brain and female reproductive organs. This review article introduces results from recent works in these fields. COX-1- or COX-2-knockout mice may provide many clues on the roles of COX-2, but may simultaneously cause unnecessary confusion in the recognition of the roles of COX-2, and this is discussed. Recently the roles of COX-2 in exudative inflammation and the anti-inflammatory effects of selective COX-2 inhibitors have been questioned. This is discussed in the text. Prostanoids mediate signals to adjacent cells to provide fine regulation of cellular function. Because of the short duration of the expression of COX-2 gene and protein, COX-2 must play some roles different from those of COX-1 gene and protein in vivo. It is not yet possible to identify all the roles of COX-2, but in some tissues, such as the kidney, the brain and others, COX-2 may be expressed constitutively, whereas the prostaglandin generation by COX-2 may replace that by COX-1 in some states (or vice-versa). Precise analyses of the expression of COX-2 may disclose fine modulation of cellular and organ functions by PGs. Several selective or preferential COX-2 inhibitors have been developed and were shown to be effective in clinical trials. Most were reported to be free of adverse gastrointestinal effects, but it should be noted that in the healing process of gastric ulcers and in sodium-restricted states, adverse effects of selective COX-2 inhibitors could be expected. Soon, with more detailed knowledge of the delicate roles of COX-2 in vivo, effective and safe application of COX-2 inhibitors should be realized.
除了在许多体细胞中组成性表达的管家型环氧化酶（COX）-1外，一种诱导型COX-2也已被描述和克隆。据报道，COX-2的诱导或存在不仅在分离的细胞中，而且在各种组织的细胞中，以及在生理和病理生理状态下均有发现，包括急性渗出性炎症、增殖性炎症、动物关节炎、类风湿性关节炎、血管生成、骨吸收、胃溃疡、结肠癌、痛觉过敏、阿尔茨海默病以及肾脏、大脑和女性生殖器官的某些状态。这篇综述文章介绍了这些领域近期研究的结果。COX-1或COX-2基因敲除小鼠可能为COX-2的作用提供许多线索，但可能同时在COX-2作用的认识上造成不必要的混淆，本文对此进行了讨论。最近，COX-2在渗出性炎症中的作用以及选择性COX-2抑制剂的抗炎作用受到了质疑。本文对此进行了讨论。前列腺素介导信号至相邻细胞以实现细胞功能的精细调节。由于COX-2基因和蛋白的表达持续时间较短，COX-2在体内必定发挥着一些与COX-1基因和蛋白不同的作用。目前尚无法确定COX-2的所有作用，但在某些组织，如肾脏、大脑等，COX-2可能组成性表达，而在某些状态下，COX-2产生的前列腺素可能替代COX-1产生的前列腺素（反之亦然）。对COX-2表达的精确分析可能揭示前列腺素对细胞和器官功能的精细调节。几种选择性或优先性COX-2抑制剂已被研发出来，并在临床试验中显示出有效性。大多数报道称其无不良胃肠道影响，但应注意的是，在胃溃疡愈合过程和钠限制状态下，选择性COX-2抑制剂可能会产生不良反应。不久之后，随着对COX-2在体内精细作用的更详细了解，COX-2抑制剂的有效和安全应用有望实现。
