Bishop-Bailey D, Pepper J R, Larkin S W, Mitchell J A
Department of Applied Pharmacology, The National Heart and Lung Institute, Imperial College of Science and Technology, London, UK.
Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1655-61. doi: 10.1161/01.atv.18.10.1655.
Two isoforms of cyclooxygenase (COX) have been identified: a constitutive isoform (COX-1), found in abundance in platelets and the vascular endothelium, and an "inflammatory" cytokine-inducible isoform (COX-2). Because COX metabolites regulate vascular smooth muscle cell (SMC) function and the interaction between the vessel and circulating components, we have investigated the possibility that COX-2 can be induced in human arterial or venous SMC. Untreated venous or arterial cells contained undetectable levels of COX-1 or COX-2 and released low levels of metabolites. After stimulation with interleukin-1beta, tumor necrosis factor-alpha, interferon-gamma, and bacterial lipopolysaccharide, both venous and arterial SMC expressed COX-2 protein and released increased amounts of prostaglandins. In addition, the induced release of PGE2 was inhibited by the COX-2-selective inhibitor, L-745,337. When cells were treated with the mixture of cytokines, venous SMC expressed greater amounts of COX-2 protein and released more prostaglandins than arterial SMC. Furthermore, when COX-2 activity was blocked by L-745,337, COX-2 expression in arterial SMC, but not in venous SMC, increased. Thus, this article describes, for the first time, that COX-2 is expressed in greater amounts in venous SMC than in arterial SMC. Moreover, we show that this "differential induction" is due to a negative-feedback pathway for COX-2 expression in arterial SMC but not in venous SMC. The ability of COX-2 activity to limit COX-2 expression in some cells but not others may contribute to the highly developed mechanisms involved in prostanoid release.
已鉴定出两种环氧化酶（COX）同工型：一种组成型同工型（COX-1），在血小板和血管内皮中大量存在，以及一种“炎症性”细胞因子诱导型同工型（COX-2）。由于COX代谢产物调节血管平滑肌细胞（SMC）功能以及血管与循环成分之间的相互作用，我们研究了COX-2能否在人动脉或静脉SMC中被诱导表达的可能性。未经处理的静脉或动脉细胞中COX-1或COX-2水平检测不到，且释放的代谢产物水平较低。在用白细胞介素-1β、肿瘤坏死因子-α、干扰素-γ和细菌脂多糖刺激后，静脉和动脉SMC均表达COX-2蛋白并释放出更多的前列腺素。此外，COX-2选择性抑制剂L-745,337可抑制PGE2的诱导释放。当细胞用细胞因子混合物处理时，静脉SMC表达的COX-2蛋白量比动脉SMC更多，释放的前列腺素也更多。此外，当COX-2活性被L-745,337阻断时，动脉SMC中的COX-2表达增加，而静脉SMC中则未增加。因此，本文首次描述了COX-2在静脉SMC中的表达量高于动脉SMC。此外，我们表明这种“差异诱导”是由于动脉SMC中存在COX-2表达的负反馈途径，而静脉SMC中不存在。COX-2活性在某些细胞而非其他细胞中限制COX-2表达的能力可能有助于前列腺素释放所涉及的高度发达的机制。
