Biosynthesis of C3 by human mesangial cells. Modulation by proinflammatory cytokines

Deposits of complement (C) components are found in the glomeruli of patients with various glomerulonephritides without detectable immunoglobulins, thus suggesting a pathogenetic role of the locally produced proteins of this system. In the present study, we have examined human mesangial cells (HMC) for their ability to secrete C3. Three different cell lines were examined and all showed a basal production of C3, which was up-regulated following stimulation with IL-1 beta. IL-6 had no direct stimulatory effect on its own, but synergized with IL-1 to induce an increased production of C3 in the culture supernatant and its relative amount was confirmed by SDS-PAGE and immunoblot. Another agonist such as lipopolysaccharide was not able to induce any significant C3 synthesis. Analysis of C3 HMC gene expression, performed by both reverse transcription-polymerase chain reaction of isolated RNA and Northern blot, confirmed the parallel increase of the specific transcript under IL-1 beta and IL-1 beta + IL-6 stimulation. From these data we conclude that production of C3 in the mesangium could have a pathophysiologic relevance.