Interleukin-1β is an autocrine growth factor of rat glomerular epithelial cells in culture

Abstract

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-1β (IL-1β) 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-1β, and the role of IL-1β 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-1β in the culture supernatants was measured by specific enzyme-linked immunosorbent assay (ELISA). IL-1β in GEC supernatants was examined by immunoblot analysis. IL-1β mRNA expression in GEC was examined by reverse transcription-polymerase chain reaction (RT-PCR). Results. IL-1β showed a mitogenic effect on GEC, while interferon-γ (IFN-γ) and heparin inhibited GEC proliferation. Moreover, GEC proliferation cultured with K1 medium was partially inhibited by anti-IL-1β neutralizing antibody. Amounts of IL-1β in the culture supernatants increased over time (24-72 h). K1 medium increased IL-1β production by GEC, while IFN-γ or heparin did not change IL-1β production. Immunoblot analysis revealed 17 kD protein of IL-1β in the concentrated GEC supernatants. RT-PCR also demonstrated mRNA expression of IL-1β in GEC. Conclusions. Our data indicate that IL-1β is an autocrine growth factor for GEC and may have an important role in the regulation of GEC proliferation.