title: Complement C3 gene expression and regulation in human glomerular epithelial cells.
abstract: Extra-hepatic synthesis of complement is thought to mediate local tissue inflammatory injury. To investigate this phenomenon in the glomerular epithelial cell (GEC), we examined the biosynthesis and regulation of gene expression of the third component of complement in isolated human GEC derived from normal tissue. Metabolic labelling and immunoprecipitation studies demonstrated that C3 protein was synthesized, processed and secreted by GEC under basal conditions. The secreted C3 alpha and beta polypeptide chains had identical electrophoretic mobilities with those of hepatic C3. Examination of cellular RNA using semi-quantitative polymerase chain reaction (PCR) showed that C3 gene expression was present in unstimulated GEC and was increased by stimulation with interferon-gamma (IFN-gamma) in a time- and dose-dependent manner. Tumour necrosis factor-alpha (TNF-alpha), while mediating an increase in monocyte U937 C3 expression, revealed no evidence of regulation of GEC C3 gene expression. These results indicate that human GEC spontaneously express the C3 gene and that increased gene expression is regulated by IFN-gamma. These observations may reflect part of a wider mechanism of protection against or mediation of local, immune-mediated tissue injury.
authors.affiliation: Renal Laboratory, United Medical School, Guy's Campus, London, U.K.
authors.forename: S H
authors.initials: SH
authors.lastname: Sacks
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Pani
authors.forename: R D
authors.initials: RD
authors.lastname: Campbell
authors.forename: J
authors.initials: J
authors.lastname: Martin
mesh_terms: D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis / Q000235:genetics*; D004848:Epithelium / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D003176:Complement C3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma