Interleukin-1 alpha enhances the biosynthesis of complement C3 and factor B by human kidney proximal tubular epithelial cells in vitro.
Local production in tubular cells of complement has been shown to occur in several kidney diseases by in situ hybridization, but the regulation at the local site during an inflammation is still unknown. In the present study, we demonstrate that human proximal tubular epithelial cells (PTEC) are able to produce complement components C3 and Factor B under non-stimulated conditions in vitro. The basal production of both was increased by 0.5 ng/ml interleukin-1 alpha (IL-1 alpha) for C3: from 95.5 +/- 4.0 ng/10(6) cells to 416.5 +/- 4.9 ng/10(6), and for Factor B: from 271 +/- 7.0 ng/10(6) cells to 457.5 +/- 7.0 ng/10(6) cells. In contrast cytokines such as TNF-alpha, IFN-gamma, IL-10 and IL-15 had no detectable effect. The upregulation by IL-1 alpha was dose- and time-dependent. The response to IL-1 alpha was shown to be mediated via the IL-1 receptor, as the addition of recombinant interleukin-1 receptor antagonist inhibited the IL-1 alpha induced complement production by more than 80%. IL-1 alpha enhanced mRNA expression of both C3 and Factor B as demonstrated by RT-PCR and dot-blot analysis. This indicated that IL-1 alpha upregulated the expression of the C3 and Factor B at the transcriptional level. We hypothesize that in vivo the production of C3 and Factor B at the local site during an inflammatory response in the kidney may be regulated by IL-1 alpha produced by inflammatory cells.
Gerritsma
J S
JS
Department of Nephrology, Leiden University Hospital, The Netherlands.
Gerritsen
A F
AF
Van Kooten
C
C
Van Es
L A
LA
Daha
M R
MR
D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis*; D011415:Complement Factor B / Q000096:biosynthesis*; D017931:DNA Primers / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D003176:Complement C3; D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D011415:Complement Factor B