Inducible cyclooxygenase may have anti-inflammatory properties
Inducible cyclooxygenase may have anti-inflammatory properties
复制标题
DOI：
10.1038/9550
复制
发表时间：
1999-06-01
期刊：
影响因子：
82.9
通讯作者：
Willoughby, DA
中科院分区：
文献类型：
--
作者：
Gilroy, DW;Colville-Nash, PR;Willoughby, DA
环加氧酶 (COX) 有两种亚型。一般来说，COX 1 在大多数组织中组成型表达，维持生理过程(1)；诱导型 COX 2 被认为是一种促炎酶，也是治疗炎症性疾病的主要靶点 (2)。在这里，我们提供了 COX 2 可能具有抗炎特性的证据。在角叉胶诱导的大鼠胸膜炎中，2小时时的主要细胞是多形核白细胞，而从24小时到48小时消退期间单核细胞占主导地位(3)。在此模型中，COX 2 蛋白表达最初在 2 小时达到峰值，与最大前列腺素 E-2 合成相关。然而，48小时时COX2表达出现第二次增加，比2小时时增加350%。矛盾的是，这与炎症消退同时发生，并与前列腺素 E-2 合成最少有关。相比之下，前列腺素D-2和15脱氧Delta(12-14)前列腺素J(2)的水平在2小时时较高，随着炎症的增加而降低，但在48小时时再次升高。选择性 COX 2 抑制剂 NS-398 和双重 COX 1/COX 2 抑制剂吲哚美辛在 2 小时内抑制炎症，但在 48 小时内显着加剧炎症。这种恶化与渗出物前列腺素 D-2 和 15 脱氧 Delta(12-14)前列腺素 J(2) 浓度降低有关，并通过更换这些前列腺素而逆转。因此，COX 2 在角叉菜胶诱导的胸膜炎（以多形核白细胞为主）的早期阶段可能是促炎性的，但在后期以单核细胞为主的阶段，COX 2 可能通过产生另一组抗炎前列腺素来帮助消退。
Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes(1); inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases(2). Here we present evidence that COX 2 may have anti-inflammatory properties. In carrageenin-induced pleurisy in rats, the predominant cells at 2 hours are polymorphonuclear leucocytes, whereas mononuclear cells dominate from 24 hours until resolution at 48 hours(3). In this model, COX 2 protein expression peaked initially at 2 hours, associated with maximal prostaglandin E-2 synthesis. However, at 48 hours there was a second increase in COX 2 expression, 350% greater than that at 2 hours. Paradoxically, this coincided with inflammatory resolution and was associated with minimal prostaglandin E-2 synthesis. In contrast, levels of prostaglandin D-2, and 15deoxy Delta(12-14)prostaglandin J(2) were high at 2 hours, decreased as inflammation increased, but were increased again at 48 hours. The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours. This exacerbation was associated with reduced exudate prostaglandin D-2 and 15deoxy Delta(12-14)prostaglandin J(2) concentrations, and was reversed by replacement of these prostaglandins. Thus, COX 2 may be pro-inflammatory during the early phase of a carrageenin-induced pleurisy, dominated by polymorphonuclear leucocytes, but may aid resolution at the later, mononuclear cell-dominated phase by generating an alternative set of anti-inflammatory prostaglandins.