title: The synthetic hydroxyproline-containing collagen analogue (Gly-Pro-Hyp)10 ameliorates acute DSS colitis.
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.
authors.forename: M M
authors.initials: MM
authors.lastname: Heimesaat
authors.forename: K
authors.initials: K
authors.lastname: Heilmann
authors.forename: A A
authors.initials: AA
authors.lastname: Kühl
authors.forename: U
authors.initials: U
authors.lastname: Erben
authors.forename: M
authors.initials: M
authors.lastname: Rühl
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: R W
authors.initials: RW
authors.lastname: Farndale
authors.forename: S
authors.initials: S
authors.lastname: Bereswill
authors.forename: U B
authors.initials: UB
authors.lastname: Göbel
authors.forename: M
authors.initials: M
authors.lastname: Zeitz
authors.forename: R
authors.initials: R
authors.lastname: Somasundaram
authors.forename: C
authors.initials: C
authors.lastname: Freise
keywords: (GPO)10; IL-10; acute DSS colitis; crinopexy; extra-intestinal immune responses; extracellular matrix; gelatinase; human IBD; in vivo; intestinal inflammation; lung; matrix metalloproteinases; pro-inflammatory cytokines; proMMP-2; proliferation