Interleukin-1 beta up-regulates the plasminogen activator/plasmin system in human mesangial cells.

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.

Urokinase-plasminogen activator is synthesized in vitro by human glomerular epithelial cells but not by mesangial cells.

The plasmin protease system may have a role in maintaining the patency of renal tubules and in regulating matrix degradation within the glomerulus. Urokinase-plasminogen activator (u-PA) is a serine protease which plays an important part in the regulation of plasmin production from plasminogen. The synthesis of u-PA by cultured human glomerular cells, in particular mesangial cells, is controversial. The present study describes the presence of u-PA in supernatants of pure cultures of human glomerular epithelial cells (EC), cocultures of EC and human mesangial cells (MC) and whole glomeruli, but not within pure cultures of MC. To confirm the synthesis of u-PA mRNA in glomerular EC, cocultures of EC and MC were tested by in situ hybridization with u-PA antisense and sense digoxigenin-labeled RNA probes. Cytoplasmic localization of u-PA mRNA was demonstrated only in the EC, thus confirming the absence of synthesis of u-PA by human mesangial cells in culture.

Effect of transforming growth factor-beta 1 on plasminogen activators and plasminogen activator inhibitor-1 in renal glomerular cells.

Recent evidence suggests that the balance between serine proteases and their inhibitors is central to the maintenance of the glomerular extracellular matrix. We have characterised the urokinase type and the tissue type plasminogen activators (PA) and their inhibitor, PAI-1, secreted from glomerular epithelial and mesangial cells as well as their co-cultures and have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) on the production of such species. Similar data were derived from whole glomeruli suspensions. TGF-beta 1 increased PAI-1 production significantly in epithelial and mesangial cells as well as in whole glomeruli, while PA production was decreased; platelet-derived growth factor had no effect. These effects are consistent with a possible decrease in matrix proteolysis, suggesting a mechanism by which TGF-beta 1 may enhance mesangial matrix accumulation, a characteristic of many forms of glomerular disease.

Renal disease and occupational exposure to organic solvents: a case referent approach.

Several recent studies have suggested that a relation may exist between exposure to occupational organic solvents and diseases of the kidney--particularly malignancy and glomerulonephritis. Two case referent studies were undertaken in the West Midlands to investigate these possibilities. In the case of renal cancer 54 live cases of biopsy proved adenocarcinoma of the kidney were compared with an equal number of community based healthy referents matched for age, sex, place of residence, and socioeconomic and ethnic grouping. For glomerulonephritis, 50 biopsy proved cases were matched in the same manner with 50 referents. Fourteen other patients were also reviewed who, on biopsy, proved not to have glomerulonephritis. For both sets of cases and their referents each individual was interviewed and a detailed account obtained of medical history and environmental exposures. Exposure to solvents was assessed independently and "blind" in a semiquantitative way by an experienced occupational hygienist. Past exposure was estimated for 10 different solvent types and 17 material types. No relation was found between exposure to solvents and renal cancer or glomerulonephritis. In the case of renal cancer the numbers studied only precluded a fourfold excess risk. For glomerulonephritis, the study, although methodologically superior to most other published studies and of similar size, was of similar power to the renal cancer investigation.

Comparison of four urine drainage systems.

An evaluation of four urine drainage systems available for use by patients with indwelling urethral catheters and prescribed by general practitioners was performed. Twenty-four patients in the community of one health district tested each system for a number of weeks. Both users and carers responsible for the management of the urine drainage system tested their acceptability and reported on preference, methods of support, ease of use and comfort. The significance of the results and their implications for nursing are discussed.