Wilson H M, Haites N E, Reid F J, Booth N A
Department of Molecular and Cell Biology, University of Aberdeen, Scotland, United Kingdom.
Kidney Int. 1996 Apr;49(4):1097-104. doi: 10.1038/ki.1996.159.
The plasminogen activators (PA), which are regulated by their specific inhibitor, PAI-1, convert the zymogen plasminogen to plasmin, a protease involved in fibrinolysis and extracellular matrix turnover. Interleukin 1 beta (IL-1) is a key cytokine released from infiltrating monocytes/macrophages during the initial stages of glomerular injury. We investigated the effects of IL-1 on the production of tissue-type plasminogen activator (t-PA), urokinase (u-PA) and PAI-1 by glomerular cells. IL-1 significantly increased the synthesis of t-PA by mesangial cells and glomerular epithelial cells (P < 0.005 for both cell types), while u-PA production was unaltered. PAI-1 in mesangial cell supernatants was significantly lower when cultured in the presence of IL-1 (p < 0.008), and the synthesis decreased in a time and dose dependent manner. The effects of IL-1 were eliminated by anti-IL-1 neutralizing antibodies. The PAI-1 sequestered in the extracellular matrix of mesangial cells was also decreased. No significant change in PAI-1 synthesis by epithelial cells was observed with exogenous IL-1. Northern blot analysis paralleled the protein results, demonstrating an increase in t-PA and a decrease in PAI-1 mRNA of mesangial cells after 6 and 24 hours stimulation with 10 U/ml IL-1. These studies suggest a role for IL-1 in regulating localized proteolysis by mesangial cells during acute inflammation.
纤溶酶原激活剂（PA）受其特异性抑制剂PAI - 1的调节，可将酶原纤溶酶原转化为纤溶酶，纤溶酶是一种参与纤维蛋白溶解和细胞外基质更新的蛋白酶。白细胞介素1β（IL - 1）是肾小球损伤初始阶段浸润的单核细胞/巨噬细胞释放的关键细胞因子。我们研究了IL - 1对肾小球细胞组织型纤溶酶原激活剂（t - PA）、尿激酶（u - PA）和PAI - 1产生的影响。IL - 1显著增加了系膜细胞和肾小球上皮细胞t - PA的合成（两种细胞类型均P < 0.005），而u - PA的产生未改变。在IL - 1存在下培养时，系膜细胞上清液中的PAI - 1显著降低（p < 0.008），且合成呈时间和剂量依赖性下降。抗IL - 1中和抗体消除了IL - 1的作用。系膜细胞细胞外基质中隔离的PAI - 1也减少。外源性IL - 1未观察到上皮细胞PAI - 1合成有显著变化。Northern印迹分析结果与蛋白质结果一致，表明用10 U/ml IL - 1刺激6小时和24小时后，系膜细胞t - PA增加，PAI - 1 mRNA减少。这些研究表明IL - 1在急性炎症期间调节系膜细胞局部蛋白水解中起作用。
