Authors:
Markus M. Heimesaat Institute of Microbiology and Hygiene, Charité, University Medicine Berlin, Berlin, Germany
Department of Micro biology and Hygiene, University Medicine Berlin, CC5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203, Berlin, Germany

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K. Heilmann Department of Biotechnology, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany

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A. A. Kühl Department of Pathology/Research Center ImmunoSciences (RCIS), Charité University Medicine Berlin, Berlin, Germany

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U. Erben Department of Pathology/Research Center ImmunoSciences (RCIS), Charité University Medicine Berlin, Berlin, Germany

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M. Rühl Department of Internal Medicine, Charité, University Medicine Berlin, Berlin, Germany

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A. Fischer Institute of Microbiology and Hygiene, Charité, University Medicine Berlin, Berlin, Germany

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R. W. Farndale Department of Biochemistry, University of Cambridge, Cambridge, UK

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S. Bereswill Institute of Microbiology and Hygiene, Charité, University Medicine Berlin, Berlin, Germany

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U. B. Göbel Institute of Microbiology and Hygiene, Charité, University Medicine Berlin, Berlin, Germany

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M. Zeitz Department of Internal Medicine, Charité, University Medicine Berlin, Berlin, Germany

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R. Somasundaram Department of Internal Medicine, Charité, University Medicine Berlin, Berlin, Germany

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C. Freise Department of Internal Medicine, Charité, University Medicine Berlin, Berlin, Germany

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Abstract

In experimental models of and humans with intestinal inflammation, increased levels of the matrix-degrading gelatinases MMP-2 and -9 in inflamed tissues can be detected. The synthetic collagen analogue (Gly-Pro-Hyp)10, (GPO)10, has been identified as a relevant binding structure for proMMP-2/-9 and promotes enzymatic activity of proMMP-2. Since targeted MMP strategies might offer promising anti-inflammatory treatment options, we for the first time studied in vivo actions exerted by (GPO)10 applying an acute dextrane sulfate sodium (DSS) induced colitis model. Seven-day intraperitoneal (GPO)10 treatment ameliorated clinical symptoms and histopathological colonic changes as compared to placebo controls with severe colitis. (GPO)10-treated mice displayed a diminished influx of neutrophils, and T- and B-lymphocytes into their colonic mucosa whereas numbers of regulatory T-cells and regenerative cells were higher as compared to placebo controls. Furthermore, IL-6 secretion was down-regulated in ex vivo colonic biopsies derived from (GPO)10-treated mice whereas higher concentrations of the anti-inflammatory cytokine IL-10 in extra-intestinal compartments such as MLN and spleen could be detected. Strikingly, influx of inflammatory cells into lungs was abolished following (GPO)10 application. We therefore propose (GPO)10 as a promising effective and safe treatment option of intestinal and extra-intestinal inflammatory conditions in humans.

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Senior editors

Editor(s)-in-Chief: Dunay, Ildiko Rita, Prof. Dr. Pharm, Dr. rer. nat., University of Magdeburg, Germany

Editor(s)-in-Chief: Heimesaat, Markus M., Prof. Dr. med., Charité - University Medicine Berlin, Germany

Editorial Board

  • Berit Bangoura, Dr. DVM. PhD,  University of Wyoming, USA
  • Stefan Bereswill, Prof. Dr. rer. nat., Charité - University Medicine Berlin, Germany
  • Dunja Bruder, Prof. Dr. rer. nat., University of Magdeburg, Germany
  • Jan Buer, Prof. Dr. med., University of Duisburg, Germany
  • Edit Buzas, Prof. Dr. med., Semmelweis University, Hungary
  • Renato Damatta, Prof. PhD, UENF, Brazil
  • Maria Deli, MD, PhD, DSc, Biological Research Center, HAS, Hungary
  • Olgica Djurković-Djaković, Prof. Phd, University of Belgrade, Serbia
  • Jean-Dennis Docquier, Prof. Dr. med., University of Siena, Italy
  • Zsuzsanna Fabry, Prof. Phd, University of Washington, USA
  • Ralf Ignatius, Prof. Dr. med., Charité - University Medicine Berlin, Germany
  • Achim Kaasch, Prof. Dr. med., Otto von Guericke University Magdeburg, Germany
  • Oliver Liesenfeld, Prof. Dr. med., Inflammatix, USA
  • Matyas Sandor, Prof. PhD, University of Wisconsin, USA
  • Ulrich Steinhoff, Prof. PhD, University of Marburg, Germany
  • Michal Toborek, Prof. PhD, University of Miami, USA
  • Susanne A. Wolf, PhD, MDC-Berlin, Germany

 

Dr. Dunay, Ildiko Rita
Magdeburg, Germany
E-mail: ildiko.dunay@med.ovgu.de

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European Journal of Microbiology and Immunology
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European Journal of Microbiology and Immunology
Language English
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2011
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ISSN 2062-509X (Print)
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