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Functional characterization of Decoy Receptor 3 in Crohn's disease
  1. Benjamin Funke (benjamin.funke{at}med.uni-heidelberg.de)
  1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
    1. Frank Autschbach (frank.autschbach{at}med.uni-heidelberg.de)
    1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
      1. Sunghee Kim (sunghee_kim_bpt{at}yahoo.com)
      1. BioPowerTech, Tuscaloosa, AL 35406, United States
        1. Felix Lasitschka
        1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
          1. Ulrike Strauch
          1. Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
            1. Gerhard Rogler
            1. Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
              1. Georg Gdynia
              1. German Cancer Research Center, Heidelberg, Germany
                1. Li Li
                1. ZMF, University of Heidelberg/Mannheim, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany
                  1. Norbert Gretz
                  1. ZMF, University of Heidelberg/Mannheim, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany
                    1. Stephan Macher-Goeppinger
                    1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
                      1. Bernd Sido
                      1. Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
                        1. Peter Schirmacher
                        1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
                          1. Stefan C Meuer
                          1. Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany
                            1. Wilfried Roth (wilfried.roth{at}med.uni-heidelberg.de)
                            1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany

                              Abstract

                              Aims: Both epithelial barrier dysfunction and apoptosis resistance of immune cells contribute to the pathogenesis of Crohn's disease (CD). The soluble Decoy receptor 3 (DcR3) acts in an anti-apoptotic manner by neutralizing the death ligand CD95L. Here, we investigated the possible involvement of DcR3 in CD.

                              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 PCR, immunoblot analysis, and immunohistochemistry. DcR3 concentrations in the serum of patients with CD were measured by enzyme-linked immunosorbent assay (ELISA). 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 CD, both at actively inflamed and non-active sites. DcR3 serum levels are significantly elevated in patients with active and non-active CD as compared to healthy controls. The expression of DcR3 in intestinal epithelial cells is induced by tumor necrosis factor-alpha (TNF-alpha). Increased DcR3 expression is associated with activation of NF-kappaB and results in protection of intestinal epithelial cells and lamina propria T cells from CD95L-induced apoptosis.

                              Conclusions: DcR3 may promote inflammation in CD by inhibiting CD95L-induced apoptosis of epithelial and immune cells as well as by inducing NF-kappaB activation.

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