Abstract
An involvement of monokines in proliferation of mesangial cells was studied in experimental mesangial cell proliferative glomerulonephritis model and in culture. Anti-rat thyrnocyte serum (ATS) recognized Thy-1.1 (-like) molecules on the glomerular mesangial cells and an intravenous administration of ATS in rats induced glomerular hypercellular lesion 4-7 days later. The glomerular lesion was composed mainly of proliferating mesangial cells as defined by immunofluorescence staining for Thy-1.1 or desmin and less of infiltraing monocytes and lymphocytes as characterized by presence of leucocyte common or Ia antigen.
The promotion of mesangial cell proliferation in the glomeruli of ATS-administered rat kidneys was supported by enhancement of 3H thymidine uptake in the glomerular cells in culture and by increase of Thy-1.1 mRNA content in the glomerular RNA. The glomeruli from the ATS-administered rats released interleukin 1 (IL-1) and tumor necrosis factor (TNF) activities in culture medium and had more IL-1β mRNA than control rat glomeruli. Recombinant human IL-1β and TNF enhanced proliferation of quiescent rat mesangial cells in culture in the simultaneous presence of low concentration of fetal bovine serum or platelet-derived growth factor, as was the case with insulin.
These results indicate that monocytes/macrophages infiltrating in glomeruli with glomerulonephritis could release monokines, such as IL-1 or TNF and these cytokines could promote proliferation of mesangial cells.
