Background: The proliferation of glomerular epithelial cells (GEC) is usually observed in crescentic glomerulonephritis. However, the regulation of GEC proliferation is not fully understood. Although it is known that interleukin-1beta (IL-1beta) has a mitogenic effect on mesangial cells and is produced by mesangial cells, the effect of this cytokine on GEC proliferation is not known. We investigated whether cultured rat GEC could produce IL-1beta, and the role of IL-1beta on GEC proliferation.
Methods: Cultured rat GEC from 24th to 36th passage were used. GEC proliferation was evaluated with a colorimetric assay using the tetrazolium salt. GEC were incubated in K1 medium for 72 h and IL-1beta in the culture supernatants was measured by specific enzyme-linked immunosorbent assay (ELISA). IL-1beta in GEC supernatants was examined by immunoblot analysis. IL-1beta mRNA expression in GEC was examined by reverse transcription-polymerase chain reaction (RT-PCR).
Results: IL-1beta showed a mitogenic effect on GEC, while interferon-gamma (IFN-gamma) and heparin inhibited GEC proliferation. Moreover, GEC proliferation cultured with K1 medium was partially inhibited by anti-IL-1beta neutralizing antibody. Amounts of IL-1beta in the culture supernatants increased over time (24-72 h). K1 medium increased IL-1beta production by GEC, while IFN-gamma or heparin did not change IL-1beta production. Immunoblot analysis revealed 17 kD protein of IL-1beta in the concentrated GEC supernatants. RT-PCR also demonstrated mRNA expression of IL-1beta in GEC.
Conclusions: Our data indicate that IL-1beta is an autocrine growth factor for GEC and may have an important role in the regulation of GEC proliferation.