Abstract | BACKGROUND: METHODS: DSS colitic mice were treated with daily pegylated GM-CSF or saline and clinical, histological, and inflammatory parameters were kinetically evaluated. Further, the role of bone marrow-derived cells in the impact of GM-CSF therapy on DSS colitis was addressed using cell transfers. RESULTS:
GM-CSF therapy reduced clinical signs of colitis and the release of inflammatory mediators. GM-CSF therapy improved mucosal repair, with faster ulcer reepithelialization, accelerated hyperproliferative response of epithelial cells in ulcer-adjacent crypts, and lower colonoscopic ulceration scores in GM-CSF-administered mice relative to untreated mice. We observed that GM-CSF-induced promotion of mucosal repair is timely associated with a reduction in neutrophil numbers and increased accumulation of CD11b(+) monocytic cells in colon tissues. Importantly, transfer of splenic GM-CSF-induced CD11b(+) myeloid cells into DSS-exposed mice improved colitis, and lethally irradiated GM-CSF receptor-deficient mice reconstituted with wildtype bone marrow cells were protected from DSS-induced colitis upon GM-CSF therapy. Lastly, GM-CSF-induced CD11b(+) myeloid cells were shown to promote in vitro wound repair. CONCLUSIONS: Our study shows that GM-CSF-dependent stimulation of bone marrow-derived cells during DSS-induced colitis accelerates colonic tissue repair. These data provide a putative mechanism for the observed beneficial effects of GM-CSF therapy in Crohn's disease.
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Authors | Eric Bernasconi, Laurent Favre, Michel H Maillard, Daniel Bachmann, Catherine Pythoud, Hanifa Bouzourene, Ed Croze, Sharlene Velichko, John Parkinson, Pierre Michetti, Dominique Velin |
Journal | Inflammatory bowel diseases
(Inflamm Bowel Dis)
Vol. 16
Issue 3
Pg. 428-41
(Mar 2010)
ISSN: 1536-4844 [Electronic] England |
PMID | 19639560
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Granulocyte-Macrophage Colony-Stimulating Factor
- Dextran Sulfate
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Topics |
- Acute Disease
- Animals
- Bone Marrow Cells
(cytology, drug effects, physiology)
- Colitis
(chemically induced, drug therapy, pathology)
- Colon
(drug effects, pathology, physiology)
- Crohn Disease
(drug therapy, pathology)
- Dextran Sulfate
(toxicity)
- Disease Models, Animal
- Female
- Granulocyte-Macrophage Colony-Stimulating Factor
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Mucous Membrane
(drug effects, pathology)
- Regeneration
(drug effects)
- Signal Transduction
(drug effects)
- Specific Pathogen-Free Organisms
- Wound Healing
(drug effects, physiology)
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