INDUCIBLE ISOFORMS OF CYCLOOXYGENASE AND NITRIC-OXIDE SYNTHASE IN INFLAMMATION
INDUCIBLE ISOFORMS OF CYCLOOXYGENASE AND NITRIC-OXIDE SYNTHASE IN INFLAMMATION
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DOI：
10.1073/pnas.91.6.2046
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发表时间：
1994-03-15
影响因子：
11.1
通讯作者：
WILLOUGHBY, DA
中科院分区：
文献类型：
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作者：
VANE, JR;MITCHELL, JA;WILLOUGHBY, DA
环氧合酶（考克斯）将花生四烯酸转化为前列腺素H-2，后者进一步代谢为前列腺素类。存在两种考克斯同工型：组成型（考克斯-1）和诱导型（考克斯-2）酶。一氧化氮通过一氧化氮合酶（NOS; EC 1.14.13.39）的同种型衍生自L-精氨酸：组成型（cNOS;钙依赖性）和诱导型（iNOS;钙非依赖性）。在这里，我们研究了诱导亚型的考克斯和NOS的急性，慢性和解决阶段的小鼠气囊模型的肉芽肿性炎症。在急性期的皮肤样品中测量考克斯和NOS活性，直至24小时。在慢性炎症和消退阶段的第3、5、7、14和21天测量肉芽肿组织中的活性。Western blot检测考克斯1和考克斯2蛋白表达。皮肤中的考克斯活性在前24小时内增加，并持续上升至第14天。考克斯-2蛋白逐渐升高，也在第14天达到峰值。考克斯-1蛋白始终保持不变。在皮肤中的第一个24小时内，iNOS活性增加，在第3天和第7天之间的肉芽肿组织中进一步增加，随后在第14天减少，在第21天进一步增加。急性期皮肤中考克斯和NOS活性的升高加强了前列腺素类的促炎作用，并提示一氧化氮也有此作用。然而，在慢性和解决阶段，考克斯和NOS活性的解离发生。因此，这些酶可能存在差异调节，这可能是由于炎症反应期间细胞因子模式的变化。
Cyclooxygenase (COX) converts arachidonic acid to prostaglandin H-2, which is further metabolized to prostanoids. Two isoforms of COX exist: a constitutive (COX-1) and an inducible (COX-2) enzyme. Nitric oxide is derived from L-arginine by isoforms of nitric-oxide synthase (NOS; EC 1.14.13.39): constitutive (cNOS; calcium-dependent) and inducible (iNOS; calcium-independent). Here we have investigated inducible isoforms of COX and NOS in the acute, chronic, and resolving stages of a murine air pouch model of granulomatous inflammation. COX and NOS activities were measured in skin samples in the acute phase, up to 24 h. Activities in granulomatous tissue were measured at 3, 5, 7, 14, and 21 days for the chronic and resolving stages of inflammation. COX-1 and COX-2 proteins were assessed by Western blot. COX activity in the skin increased over the first 24 h and continued to rise up to day 14. COX-2 protein rose progressively, also peaking at day 14. COX-1 protein remained unaltered throughout. The iNOS activity increased over the first 24 h in the skin, with a further major increase in the granulomatous tissue between days 3 and 7, followed by a decrease at day 14 and a further increase at day 21. The rise in COX and NOS activities in the skin during the acute phase reinforces the proinflammatory role for prostanoids and suggests one also for nitric oxide. However, in the chronic and resolving stages, a dissociation of COX and NOS activity occurred. Thus, there may be differential regulation of these enzymes, perhaps due to the changing pattern of cytokines during the inflammatory response.