We have previously shown in inbred strains of mice which naturally dev
elop systemic lupus erythematosus that kidney C3, C2, C4 and factor B
gene expression increases coincidently with the occurrence of glomerul
onephritis, suggesting that local tissue complement gene expression co
uld contribute to the pathogenesis of immune complex injury. In this s
tudy, we investigated the synthesis of complement proteins in glomerul
ar epithelial cells (GECs) and its regulation. Using biosynthetic labe
lling, immunoprecipitation and sodium dodecyl sulfate-poly acrylamide
gel electrophoresis, we demonstrated that GECs synthesized C1r, C1s, C
1 inhibitor, C3, C2 and factor B. Interferon-gamma induced increases i
n the synthesis of all these proteins. Both factor B and C3 proteins w
ere increased following addition of either IL-1 beta, IL-6 or TNF-alph
a to GEC cultures; however, these cytokines did not increase either C2
, C1r, C1s or C1-inhibitor biosynthesis. Lipopolysaccharide affected t
he biosynthesis of these proteins in a similar way. A semiquantitative
analysis of the mRNA expression of some of these proteins by reverse-
transcriptase polymerase chain reaction showed that these cytokine eff
ects were pretranslational as there was enhancement of factor B mRNA e
xpression by IL-1, TNF-alpha, IFN-gamma, IL-6 and endotoxin, but only
IFN-gamma enhanced C1-inhibitor and C4 mRNA expression. These results
may be of significance in the immunopathogenesis of glomerulonephritis
, where it is likely that local complement production in GECs is indep
endently regulated by cytokines, derived from resident glomerular mesa
ngial cells or infiltrating monocyte/macrophages and T cells.