Abstract
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 1β (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 elimininated 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.
Original language | English |
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Pages (from-to) | 1097-1104 |
Number of pages | 8 |
Journal | Kidney International |
Volume | 49 |
Issue number | 4 |
DOIs | |
Publication status | Published - 30 Jan 1996 |