Campbell I K, Last K, Novak U, Lund L R, Hamilton J A
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Biochem Biophys Res Commun. 1991 Jan 15;174(1):251-7. doi: 10.1016/0006-291x(91)90513-7.
Human articular cartilage and chondrocyte monolayers in culture constitutively produced plasminogen activator inhibitor-1 (PAI-1) protein and mRNA, as assessed by a specific enzyme-linked immunosorbent assay and Northern blotting analysis, respectively. Recombinant human interleukin-1 (IL-1) invoked a dose-dependent inhibition of PAI-1 production in both cartilage and chondrocyte cultures. The inhibitory effect of IL-1 was observed between 2-8h after addition of the cytokine, while the optimal dose was between 10-100U/ml IL-1 alpha (57-570pM IL-1 alpha). Results obtained by Northern analysis of chondrocyte total RNA reflected those found for the PAI-1 antigen, namely, that nontreated chondrocytes showed PAI-1 mRNA which was reduced by IL-1 treatment. To our knowledge, this is the first report where IL-1 has been found to inhibit PAI-1 expression. Since IL-1 has been shown before to cause human cartilage destruction and a correlated change in plasminogen activator activity, it could be that a concomitant reduction in PAI-1 levels by IL-1 may be significant in the control of these changes in cartilage.
通过特异性酶联免疫吸附测定和Northern印迹分析评估发现，培养的人关节软骨和软骨细胞单层组成性地产生纤溶酶原激活物抑制剂-1（PAI-1）蛋白和mRNA。重组人白细胞介素-1（IL-1）在软骨和软骨细胞培养物中均引起PAI-1产生的剂量依赖性抑制。在添加细胞因子后2-8小时观察到IL-1的抑制作用，而最佳剂量为10-100U/ml IL-1α（57-570pM IL-1α）。通过对软骨细胞总RNA进行Northern分析得到的结果反映了PAI-1抗原的情况，即未处理的软骨细胞显示出PAI-1 mRNA，而IL-1处理使其减少。据我们所知，这是首次报道IL-1可抑制PAI-1表达。由于之前已表明IL-1会导致人软骨破坏以及纤溶酶原激活物活性的相关变化，因此IL-1使PAI-1水平同时降低可能对控制软骨中的这些变化具有重要意义。
