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Induced B7-H1 expression on human renal tubular epithelial cells by the sublytic terminal complement complex C5b-9.
- Source :
-
Molecular immunology [Mol Immunol] 2009 Jan; Vol. 46 (3), pp. 375-83. Date of Electronic Publication: 2008 Dec 09. - Publication Year :
- 2009
-
Abstract
- The co-inhibitory molecule B7-H1 has been broadly detectable on human inflammatory renal tubular epithelial cells (TECs) and is proposed to limit tubular damage through down-regulation of tubulointerstitial infiltration T cell activation. Nevertheless, factors that initiate B7-H1 expression on TECs remain unclarified. The terminal complement complex C5b-9, which deposits diffusely on tubules and glomerules of diseased kidneys, is now recognized as a mediator that triggers cellular activation rather than inducing cell death. Whether the up-regulation of B7-H1 on tubules is also induced by C5b-9 is uncertain. Here, after assembling functional sublytic C5b-9 on the membranes of TECs based on purified complement components, we found that B7-H1 gene transcription and protein synthesis was enhanced by C5b-9. Promoter constructs in a luciferase assay, site-directed mutagenesis and laser scanning confocal microscopy assay (LSCM) revealed that the transcription factor NF-kappaB is primarily responsible for C5b-9-mediated B7-H1 expression. To further detect the physiologic function of B7-H1, triggering B7-H1 with its agonist mAb (clone 5H1) profoundly enhanced Fas expression on C5b-9-treated TECs and thus induced TEC apoptosis. Interestingly, pretreatment of TECs with Fas blocking antibodies prevented this effect. Our results propose that C5b-9 regulates tubular pathogenesis in glomerulonephritis or other renal autoimmune diseases, possibly through enhances cell apoptosis mediated by B7-H1 signals, in addition to it directly promotes tubular damage.
- Subjects :
- Antigens, CD metabolism
Apoptosis
B7-H1 Antigen
Base Sequence
Blotting, Western
Cell Line
Epithelial Cells cytology
Fas Ligand Protein metabolism
Flow Cytometry
Humans
Kidney Tubules metabolism
Microscopy, Confocal
Molecular Sequence Data
NF-kappa B metabolism
Promoter Regions, Genetic genetics
RNA, Messenger genetics
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription, Genetic
fas Receptor metabolism
Antigens, CD genetics
Complement Membrane Attack Complex metabolism
Epithelial Cells metabolism
Kidney Tubules cytology
Subjects
Details
- Language :
- English
- ISSN :
- 0161-5890
- Volume :
- 46
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 19081139
- Full Text :
- https://doi.org/10.1016/j.molimm.2008.10.026