Cytokine-regulated production of the major histocompatibility complex class-III-encoded complement proteins factor B and C4 by human glomerular mesangial cells.
Local production of complement within normal or diseased kidneys could be of importance during local inflammatory reactions. In the present study, we demonstrate that human MCs are able to synthesize the MHC class-III-encoded complement proteins factor B and C4 in vitro. This synthesis is strongly upregulated following stimulation with cytokine-containing supernatants of activated peripheral blood mononuclear cells. All primary cell lines tested so far are able to synthesize factor B and C4 after stimulation. To determine more specifically whether defined cytokines are able to enhance factor B and C4 complement production, MCs were stimulated with IL-1 alpha, IFN-gamma, and TNF-alpha. Factor B synthesis was increased in a dose-dependent fashion by IL-1 alpha, TNF-alpha, and IFN-gamma, whereas C4 synthesis was only upregulated by IFN-gamma. Furthermore, factor B synthesis was upregulated after stimulation with IFN-alpha, -beta, and -gamma and C4 synthesis only by IFN-gamma. The synthesis of factor B and C4 was inhibited by cycloheximide, suggesting de novo protein synthesis. The cytoplasmic localization of both components was shown by immunofluorescence studies. Northern and dot blot analysis revealed induction of factor B and C4 mRNA after stimulation with cytokines.
Timmerman
J J
JJ
Department of Nephrology and Rheumatology, Leiden University Hospital, The Netherlands.
Verweij
C L
CL
van Gijlswijk-Janssen
D J
DJ
van der Woude
F J
FJ
van Es
L A
LA
Daha
M R
MR
D002478:Cells, Cultured; D003181:Complement C4 / Q000096:biosynthesis* / Q000187:drug effects; D011415:Complement Factor B / Q000096:biosynthesis* / Q000187:drug effects; D016207:Cytokines / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D003181:Complement C4; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons; D011415:Complement Factor B