Kojima S, Vernooy R, Moscatelli D, Amanuma H, Rifkin D B
Department of Cell Biology, New York University Medical School, New York 10016.
J Cell Physiol. 1995 Apr;163(1):210-9. doi: 10.1002/jcp.1041630124.
The activation of latent transforming growth factor-beta (TGF-beta) by vascular endothelial cells (ECs) is regulated by cellular plasminogen activator (PA)/plasmin, transglutaminase (TGase), and latent TGF-beta levels. Because lipopolysaccharide (LPS) has been reported to reduce EC surface plasmin levels by increasing the production of the inhibitor of PA, PA inhibitor-1 (PAI-1), we have tested whether LPS might suppress latent TGF-beta activation in ECs using two different systems, namely, bovine aortic ECs (BAECs) cocultured with smooth muscle cells (SMCs) and BAECs treated with retinol. BAECs were either cocultured with SMCs after treatment with 15 ng/ml LPS or were treated with 2 microM retinol and/or 10 ng/ml LPS, and the expression of PA, surface plasmin, TGase, and the amounts of active and latent TGF-beta secreted into the culture medium were measured. The downregulation of surface PA/plasmin levels with LPS was accompanied by a profound decline of both TGase and latent TGF-beta expression as well as the suppression of surface activation of latent TGF-beta. The effect was dependent on the concentration of LPS and on treatment time. The formation of TGF-beta did not occur in cells maintained in LPS-contaminated culture medium.
血管内皮细胞（ECs）对潜伏转化生长因子-β（TGF-β）的激活受细胞纤溶酶原激活物（PA）/纤溶酶、转谷氨酰胺酶（TGase）以及潜伏TGF-β水平的调节。由于据报道脂多糖（LPS）可通过增加PA抑制剂-1（PAI-1）的产生来降低EC表面纤溶酶水平，因此我们使用两种不同系统，即与平滑肌细胞（SMCs）共培养的牛主动脉内皮细胞（BAECs）和用视黄醇处理的BAECs，来测试LPS是否会抑制ECs中潜伏TGF-β的激活。BAECs在用15 ng/ml LPS处理后与SMCs共培养，或者用2 μM视黄醇和/或10 ng/ml LPS处理，然后测量PA、表面纤溶酶、TGase的表达以及分泌到培养基中的活性和潜伏TGF-β的量。LPS使表面PA/纤溶酶水平下调的同时，TGase和潜伏TGF-β的表达也显著下降，并且潜伏TGF-β的表面激活受到抑制。该效应取决于LPS的浓度和处理时间。在受LPS污染的培养基中培养的细胞未发生TGF-β的形成。
