Burke-Gaffney A, Keenan A K
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Agents Actions. 1993;38 Spec No:C83-5. doi: 10.1007/BF01991145.
The effects of dexamethasone (DEX) and N omega-nitro-L-arginine methyl ester (L-NAME) on the tumour necrosis factor-alpha (TNF-alpha)-induced increase in permeability of human umbilical vein endothelial cell (HUVEC) monolayer to [125I] labelled bovine serum albumin (BSA) were examined. Preincubation of HUVEC monolayers with DEX (1 microM, 2h) completely abolished the effect of TNF-alpha (5 ng/ml, 18 h). Administration of DEX 2 h after TNF-alpha also reduced the effect of TNF-alpha while L-NAME (5 ng/ml, 1 mM, 18 h) had no significant effect. The observed inhibition of the TNF-alpha-induced permeability increase on preincubation with DEX would suggest a role for nitric oxide (NO) in mediating the permeability response. However, this is not confirmed by the experiments with L-NAME. The inhibition caused by DEX administered after TNF-alpha would suggest alternative mechanisms by which DEX may be acting in addition to inhibition of NO synthase induction.
研究了地塞米松（DEX）和N-ω-硝基-L-精氨酸甲酯（L-NAME）对肿瘤坏死因子-α（TNF-α）诱导的人脐静脉内皮细胞（HUVEC）单层对[125I]标记牛血清白蛋白（BSA）通透性增加的影响。用DEX（1μM，2小时）预孵育HUVEC单层可完全消除TNF-α（5 ng/ml，18小时）的作用。在TNF-α作用2小时后给予DEX也可降低TNF-α的作用，而L-NAME（5 ng/ml，1 mM，18小时）则无显著作用。预先用DEX孵育观察到的对TNF-α诱导的通透性增加的抑制作用表明一氧化氮（NO）在介导通透性反应中起作用。然而，L-NAME实验并未证实这一点。TNF-α后给予DEX所引起的抑制作用表明，除了抑制一氧化氮合酶诱导外，DEX可能通过其他机制发挥作用。
