Pulmonary epithelial cell urokinase-type plasminogen activator. Induction by interleukin-1 beta and tumor necrosis factor-alpha.

摘要: Diffuse alveolar damage, presenting clinically as adult respiratory distress syndrome, is characterized initially by widespread intra-alveolar fibrin deposition. Alveolar epithelial cells play a central role in the subsequent repair process. We have recently shown that capacity to promote fibrinolysis (Marshall, B. C., Sageser, D. S., Rao, N. V., Emi, M., and Hoidal, J. R. (1990) Biol. Chem. 265, 8198-8204) may therefore directly participate extensive remodeling follows acute lung injury. Because tissue process occurs an inflammatory setting, we investigated effects of mediators on urokinase-type plasminogen activator (u-PA) expression pulmonary cells. found interleukin-1 beta (IL-1 beta) tumor necrosis factor-alpha (TNF-alpha) upregulated PA activity A549 human Biosynthetic labeling immunoprecipitation showed both cytokines caused marked accumulation newly synthesized u-PA. Northern blot analyses demonstrated IL-1 TNF-alpha induced relatively rapid u-PA mRNA which did not require de novo protein synthesis was substantially inhibited glucocorticoids. Nuclear run-off transcription studies transcriptional activation gene. While were qualitatively similar, some differences emerged. Most notably, led more sustained than beta. In contrast their expression, had minimal effect inhibitor-1 expression. These TNF-alpha, known key injury inflammation, lysis epithelium, thereby aiding restoration normal architecture.