Akarasereenont P, Mitchell J A, Bakhle Y S, Thiemermann C, Vane J R
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Eur J Pharmacol. 1995 Jan 24;273(1-2):121-8. doi: 10.1016/0014-2999(94)00680-6.
Endotoxin causes the expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2. We have compared the ability of endotoxin to increase the activities of these enzymes in bovine aortic endothelial cells and the macrophage cell line (J774.2). Endotoxin (1 microgram ml-1; for 24 h) caused a time-dependent increase in the accumulation of cyclooxygenase metabolites from endogenous arachidonic acid, in both cell types. Cyclooxygenase activity towards exogenous arachidonic acid (30 microM; for 15 min) was also increased in both cell types. Endothelial cells and macrophages also contained comparable amounts of cyclooxygenase-2 protein after incubation with endotoxin for 24 h which was prevented by pretreatment with cycloheximide (10 micrograms ml-1; 30 min prior to endotoxin). Endotoxin for 24 h caused a time-dependent increase in nitrite accumulation in macrophages, but not in endothelial cells. Thus, endotoxin increased cyclooxygenase activity and induced cyclooxygenase-2 protein in endothelial cells and macrophages. Endotoxin also increased NO synthase activity in macrophages, but not in endothelial cells.
内毒素可导致诱导型一氧化氮（NO）合酶和环氧化酶-2的表达。我们比较了内毒素在牛主动脉内皮细胞和巨噬细胞系（J774.2）中增加这些酶活性的能力。内毒素（1微克/毫升；作用24小时）导致两种细胞类型中内源性花生四烯酸的环氧化酶代谢产物积累随时间增加。两种细胞类型对外源花生四烯酸（30微摩尔；作用15分钟）的环氧化酶活性也增加。用内毒素孵育24小时后，内皮细胞和巨噬细胞中环氧化酶-2蛋白含量相当，而用环己酰亚胺（10微克/毫升；在内毒素处理前30分钟）预处理可阻止这种情况。内毒素作用24小时导致巨噬细胞中亚硝酸盐积累随时间增加，但在内皮细胞中未出现这种情况。因此，内毒素增加了内皮细胞和巨噬细胞中的环氧化酶活性并诱导了环氧化酶-2蛋白。内毒素还增加了巨噬细胞中的NO合酶活性，但在内皮细胞中未增加。
