Interferon-gamma regulation of C4 gene expression in cultured human glomerular epithelial cells

Abstract

The fourth component of human complement is mainly produced in liver, but extrahepatic gene expression has been reported in human renal tissue and other tissues, and is thought to contribute to the inflammatory reaction in local tissue. To identify the cellular origin of C4 synthesis in human kidney, we studied C4 gene expression and regulation by interferon-gamma (IFN-gamma) and C4 protein biosynthesis in isolated glomerular epithelial cells. cDNA/polymerase chain reaction analysis showed that C4 transcripts are present in glomerular epithelial cells (GEC), and that gene expression is up-regulated by IFN-gamma. Metabolic labeling studies showed that GEC synthesize and secrete C4 as three polypeptide chains of approximately 90, 70, and 30 kDa, which correspond to the bands produced by hepatoma cells. These results suggest that the fourth component of complement is produced by GEC. The GEC has an important role in the maintenance of glomerular barrier function, which is lost in a number of complement-dependent conditions; glomerular epithelial synthesis of C4 could have a bearing on the possible physiological or pathological roles of complement under different circumstances.