Bishop-Bailey D, Burke-Gaffney A, Hellewell P G, Pepper J R, Mitchell J A
Department of Applied Pharmacology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):44-7. doi: 10.1006/bbrc.1998.8966.
Prostaglandins are well characterised inflammatory mediators, whose formation is regulated by constitutive (COX-1) or inducible (COX-2) isoforms of cyclo-oxygenase. We have previously demonstrated that IL-1 beta causes an induction of COX-2 in human vascular smooth muscle (1). This present study investigates the ability of different cytokines to induce ICAM-1 and VCAM-1 on human vascular smooth muscle, and tests whether co-induced COX-2 would regulate their expression. IL-1 beta induced ICAM-1, and COX activity, while it had no affect on VCAM-1. Conversely, IL-4 induced VCAM-1, while it had no effect on PGE2 release or ICAM-1 expression. Inhibition of IL-1 beta induced COX-2 and elevated ICAM-1 expression, an effect reversed by exogenous PGE2. Furthermore, IL-1 beta inhibited IL-4 induced VCAM-1 expression, which was also reversed by COX-2 inhibition. These results demonstrate that COX-2 limits adhesion molecule expression on human vascular smooth muscle cells and suggest that COX-2 can play a protective role in cardiovascular and inflammatory diseases.
前列腺素是特征明确的炎症介质，其形成受环氧化酶的组成型（COX-1）或诱导型（COX-2）同工型调控。我们之前已证明，白细胞介素-1β可诱导人血管平滑肌中COX-2的表达（1）。本研究调查了不同细胞因子诱导人血管平滑肌上细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的能力，并测试了共同诱导的COX-2是否会调节它们的表达。白细胞介素-1β诱导了ICAM-1和COX活性，而对VCAM-1没有影响。相反，白细胞介素-4诱导了VCAM-1，而对前列腺素E2（PGE2）释放或ICAM-1表达没有影响。抑制白细胞介素-1β诱导的COX-2可提高ICAM-1表达，外源性PGE2可逆转这一效应。此外，白细胞介素-1β抑制白细胞介素-4诱导的VCAM-1表达，COX-2抑制也可逆转这一效应。这些结果表明，COX-2可限制人血管平滑肌细胞上黏附分子的表达，并提示COX-2在心血管疾病和炎症性疾病中可能发挥保护作用。
