C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells
- 1 September 1993
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 93 (3), 411-417
- https://doi.org/10.1111/j.1365-2249.1993.tb08193.x
Abstract
SUMMARY: The glomerular mesangial cell (GMC) plays a key role in the maintenance of glomerular structure and function and in the mediation of glomerular injury. To explore the potential of this cell to produce complement and react to local inflammatory signals, we studied the synthesis and regulation of the third and fourth components of complement in cultured human GMC. Using metabolic labelling and immunoprecipitation, we found that C3 and C4 polypeptide chains were synthesized and secreted by GMC. Interferon-gamma (IFN-γ) led to an increase in C4 protein synthesis, but not C3 synthesis. There was a corresponding increase in C4 mRNA in IFN-γ-activated cells, but no increase in C3 mRNA, as determined by semi-quantitative polymerase chain reaction (PCR) estimation. These results demonstrate that human GMC can synthesize C3 and C4 proteins, and that regulation of expression of the C4 gene is mediated by IFN-γ. We hypothesize that GMC production of complement could influence the clearance of immune aggregates by the kidney and the mediation of glomerular injury.Keywords
This publication has 44 references indexed in Scilit:
- Interleukin-1β stimulates human mesangial cells to synthesize and release interleukins-6 and -8Kidney International, 1991
- Biology of complement: the overtureImmunology Today, 1991
- Counterregulatory effects of interferon-gamma and endotoxin on expression of the human C4 genes.JCI Insight, 1990
- The role of mesangial cells in glomerular pathologyPathology, 1990
- Biosynthesis of Complement C4 Messenger RNA in Normal Human KidneyNephron, 1989
- Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture.The Journal of Experimental Medicine, 1988
- The Role of Complement and Its Receptor in the Elimination of Immune ComplexesNew England Journal of Medicine, 1986
- Identification and structural characterization of two incompletely processed forms of the fourth component of human complement.JCI Insight, 1983
- Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes.The Journal of Experimental Medicine, 1980
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970