Interleukin-1α enhances the biosynthesis of complement C3 and factor B by human kidney proximal tubular epithelial cells in vitro

Abstract

Local production in tubular cells of complement has been shown to occur in several kidney diseases by in situ hybridization, but the regulation at the local site during an inflammation is still unknown. In the present study, we demonstrate that human proximal tubular epithelial cells (PTEC) are able to produce complement components C3 and Factor B under non-stimulated conditions in vitro. The basal production of both was increased by 0.5 ng/ml interleukin-1α (IL-1α) for C3: from 95.5 ± 4.0 ng/10 6 cells to 416.5 ± 4.9 ng/10 6, and for Factor B: from 271 ± 7.0 ng/10 6 cells to 457.5 ± 7.0 ng/10 6 cells. In contrast cytokines such as TNF-α, IFN-γ, IL-10 and IL-15 had no detectable effect. The upregulation by IL-1α was dose- and time-dependent. The response to IL-1α was shown to be mediated via the IL-1 receptor, as the addition of recombinant interleukin-1 receptor antagonist inhibited the IL-1α induced complement production by more than 80%. IL-1α enhanced mRNA expression of both C3 and Factor B as demonstrated by RT-PCR and dot-blot analysis. This indicated that IL-1α upregulated the expression of the C3 and Factor B at the transcriptional level. We hypothesize that in vivo the production of C3 and Factor B at the local site during an inflammatory response in the kidney may be regulated by IL-1α produced by inflammatory cells.