Interferon-gamma induces biosynthesis of complement components C2, C4 and factor H by human proximal tubular...

In a previous study the authors demonstrated that the production of complement component C4 by human kidney proximal tubular epithelial cells (PTEC) is upregulated by interferon gamma (IFN-gamma). In the present study the authors describe that PTEC in culture express both mRNA and protein of the IFN-gamma receptor complex, and that culture of PTEC with 1000 U/ml IFN-gamma for 72 h results in enhanced production not only of C4 (36.1 ng/10(6) cells), but also of C2 (10.8 ng/10(6) cells) and Factor H (17.5 ng/10(6) cells). Unstimulated PTEC produced 0.5 ng/10(6) cells, 0.5 ng/10(6) cells and 0.4 ng/10(6) cells of C2, C4 and Factor H, respectively. The upregulation of the three complement components was dose- and time-dependent and specific for IFN-gamma because the effect of IFN-gamma was abolished by a monoclonal antibody directed against IFN-gamma. Furthermore no effect of other cytokines was observed. The regulation of synthesis of C2, C4 and Factor H occurred at the transcriptional level as shown by semi-quantitative RT-PCR and dot-blot analysis. Taken together with the observation that in normal kidney tissue the tubuli express IFN-gamma receptor alpha-chain and a signal transducing protein, the present study implies that enhanced production of complement by PTEC may occur during a local immune response by in situ generation of IFN-gamma by infiltrating T-cells in the interstitium of the kidney.