Interferon-gamma induces biosynthesis of complement components C2, C4 and factor H by human proximal tubular epithelial cells.
In a previous study the authors demonstrated that the production of complement component C4 by human kidney proximal tubular epithelial cells (PTEC) is upregulated by interferon gamma (IFN-gamma). In the present study the authors describe that PTEC in culture express both mRNA and protein of the IFN-gamma receptor complex, and that culture of PTEC with 1000 U/ml IFN-gamma for 72 h results in enhanced production not only of C4 (36.1 ng/10(6) cells), but also of C2 (10.8 ng/10(6) cells) and Factor H (17.5 ng/10(6) cells). Unstimulated PTEC produced 0.5 ng/10(6) cells, 0.5 ng/10(6) cells and 0.4 ng/10(6) cells of C2, C4 and Factor H, respectively. The upregulation of the three complement components was dose- and time-dependent and specific for IFN-gamma because the effect of IFN-gamma was abolished by a monoclonal antibody directed against IFN-gamma. Furthermore no effect of other cytokines was observed. The regulation of synthesis of C2, C4 and Factor H occurred at the transcriptional level as shown by semi-quantitative RT-PCR and dot-blot analysis. Taken together with the observation that in normal kidney tissue the tubuli express IFN-gamma receptor alpha-chain and a signal transducing protein, the present study implies that enhanced production of complement by PTEC may occur during a local immune response by in situ generation of IFN-gamma by infiltrating T-cells in the interstitium of the kidney.
Gerritsma
J S
JS
Department of Nephrology, Leiden University Hospital, The Netherlands. Gerritsma@Rullf2.Medfac.leidenuniv.nl
Gerritsen
A F
AF
De Ley
M
M
van Es
L A
LA
Daha
M R
MR
D003175:Complement C2 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D003181:Complement C4 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017242:Complement Factor H / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000096743:Interferon gamma Receptor
D003175:Complement C2; D003181:Complement C4; D017242:Complement Factor H; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C493495:CFH protein, human