The synthetic hydroxyproline-containing collagen analogue (Gly-Pro-Hyp)10ameliorates acute DSS colitis
| Autor: | Markus M. Heimesaat, Martin Zeitz, Ulf B. Göbel, R. Farndale, Christian Freise, Stefan Bereswill, Katja Heilmann, M. Rühl, R. Somasundaram, Ulrike Erben, Anja A. Kühl, Andre Fischer |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | European Journal of Microbiology and Immunology. 2:192-200 |
| ISSN: | 2062-8633 2062-509X |
| DOI: | 10.1556/eujmi.2.2012.3.4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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