Growth Factor for Mesangial Cell : Tumor Necrosis Factor and Interleukin 1

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Impairment of glomerular filtration due to glomerular disease is considered to be caused by prolife ration of mesangial cells and increase of mesangial matrix. In the present study, a participation of cytokines, especially macrophage-derived cytokines such as tumor necrosis factor (TNF) and interleukin 1(IL-1) in the proliferation of mesangial cells was examined in vivo and in vitro.(1) Mesangial cell proliferative glomerulonephritisIntravenous administration of anti-thymocyte serum induced mesangial proliferative lesion after 4 days. Proliferation of mesangial cells was verified by increase in the number of cells satined with anti-Thy-1.1 and anti-desmin antibodies. Several macrophages were also identified in the proliferative lesion by anti-rat macrophage monoclonal antibody (ED-1). The glomeruli isolated from the rats with ATS-induced mesangial cell proliferative glomerulonephritis secreted TNF and IL-1 in culture significantly more than control glomeruli. Further, RNA extracted from the nephritic glomeruli contained more mRNA for IL-1 than control glomeruli when examined by dot blot hybridization. By in situ hybridization IL-1mRNA expressing cells were visualized in the glomeruli with ATS-induced mesangial cell proliferative glomerulonephritis and human nephritic glomeruli.(2) Mesangial cell proliferation in cultureRat mesangial cells were cultured in RPMI 1640 medium supplemented with0.5% fetal bovine serum (FBS) for 6 days to arrest these cells in G0/G1 phase of cell cycle. Both recombinant human TNF (2-200 ng/ml) and IL-1beta (0.1-2.5 ng/ml) facilitate uptake of trithiated thymidine in the presence of FBS (0.625-2.5%) or plateletーderived growth factor (0.8-4 ng/ml). These results strongly suggested that TNF or IL-1 released in inflammatory glomeruli stimulated mesangial cells to proliferate.