Arai T, Kelly S A, Brengman M L, Takano M, Smith E H, Goldschmidt-Clermont P J, Bulkley G B
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, USA.
Biochem J. 1998 May 1;331 ( Pt 3)(Pt 3):853-61. doi: 10.1042/bj3310853.
Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor alpha (TNF-alpha) in vitro. TNF-alpha upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-alpha was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-alpha. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-alpha to induce ICAM-1 expression in endothelium in vitro.
促炎细胞因子上调内皮黏附分子表达，从而引发微血管炎症反应。我们重新评估了活性氧代谢产物（ROMs）在体外肿瘤坏死因子α（TNF-α）信号传导上调内皮细胞细胞间黏附分子1（ICAM-1）中的作用。细胞可渗透的抗氧化剂或腺病毒介导的细胞内铜锌超氧化物歧化酶过表达可抑制TNF-α对内皮细胞ICAM-1表达的上调，但细胞不可渗透的抗氧化剂、超氧化物歧化酶和/或过氧化氢酶的外源（细胞外）给药则不能。NADH脱氢酶、细胞色素bc1复合体和NADPH氧化酶的抑制剂也可抑制这种ICAM-1上调。然而，使用四种不同的敏感ROM检测方法均未观察到TNF-α刺激后细胞净ROM生成有可测量的增加。此外，外源性或内源性ROM生成的刺激并未上调ICAM-1，也未增强TNF-α对ICAM-1的上调。这些发现表明，细胞内产生的ROMs的环境背景通量，而非其净增量生成，对于TNF-α在体外诱导内皮细胞中ICAM-1表达是必要的。
