Functional characterisation of decoy receptor 3 in Crohn’s disease
- B Funke1,
- F Autschbach1,
- S Kim2,
- F Lasitschka1,3,
- U Strauch4,
- G Rogler4,
- G Gdynia1,5,
- L Li6,
- N Gretz6,
- S Macher-Goeppinger1,
- B Sido7,
- P Schirmacher1,
- S C Meuer3,
- W Roth1,5
- 1Institute of Pathology, University Hospital Heidelberg, Germany
- 2BioPowerTech, Tuscaloosa, Alabama, USA
- 3Institute of Immunology, University Hospital Heidelberg, Germany
- 4Department of Internal Medicine I, University of Regensburg, Germany
- 5German Cancer Research Center, Heidelberg, Germany
- 6ZMF, University of Heidelberg/Mannheim, Mannheim, Germany
- 7Department of Surgery, University Hospital Heidelberg, Germany
- Dr W Roth, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany; Wilfried.Roth{at}med.uni-heidelberg.de
- Revised 21 October 2008
- Accepted 18 November 2008
- Published Online First 27 November 2008
Abstract
Aims: Both epithelial barrier dysfunction and apoptosis resistance of immune cells contribute to the pathogenesis of Crohn’s disease. The soluble decoy receptor 3 (DcR3) acts in an anti-apoptotic manner by neutralising the death ligand CD95L. Here, we investigated the possible involvement of DcR3 in Crohn’s disease.
Methods: The epithelial fraction of human small intestinal mucosa samples was obtained by laser microdissection. Expression of DcR3 was examined by global gene expression profiling, quantitative reverse transcription polymerase chain reaction, immunoblot analysis, and immunohistochemistry. DcR3 concentrations in the serum of patients with Crohn’s disease were measured by enzyme-linked immunosorbent assay. Apoptosis assays were performed to study the effects of DcR3 in intestinal epithelial cells and lamina propria T cells.
Results: DcR3 is over-expressed in the epithelial layer of ileum specimens in patients with Crohn’s disease, both at actively inflamed and non-active sites. DcR3 serum levels are significantly elevated in patients with active and non-active Crohn’s disease as compared to healthy controls. The expression of DcR3 in intestinal epithelial cells is induced by tumour necrosis factor α. Increased DcR3 expression is associated with activation of nuclear factor kappa B (NF-κB) and results in protection of intestinal epithelial cells and lamina propria T cells from CD95L-induced apoptosis.
Conclusions: DcR3 may promote inflammation in Crohn’s disease by inhibiting CD95L-induced apoptosis of epithelial and immune cells as well as by inducing NF-κB activation.
Footnotes
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Competing interests: None.
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Funding: This project was supported by grants from the German Research Foundation to FA, BS and SCM (DFG; SFB 405/project B6) and from the Deutsche Krebshilfe to WR (German Cancer Aid, Max Eder Program).
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Ethics approval: The use of human tissues or sera for the study was approved by the local ethics committee of the University Hospital Heidelberg, Germany, and the University of Regensburg, Germany on 21 October 2005.
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‣ A 14-part supplement (methods, figures and tables) is published online only at http://gut.bmj.com/content/vol58/issue4
