Abstract | BACKGROUND: METHODS: RESULTS:
GM-CSF ameliorates acute DSS-induced colitis, resulting in significantly improved clinical parameters and histology. Microarray analysis showed reduced expression of proinflammatory genes including TNF-alpha and IL1-beta; the results were further confirmed by real-time reverse-transcriptase polymerase chain reaction and serum Bio-plex analysis. GM-CSF treatment significantly expands pDCs and type 1 IFN production. Administration of mAb 440c completely blocked the therapeutic effect of GM-CSF. GM-CSF is also effective in RAG1(-/-) mice, demonstrating activity-independent effects on T and B cells. IFN-beta administration mimics the therapeutic effect of GM-CSF in DSS-treated mice. GM-CSF increases systemic and mucosal type 1 IFN expression and exhibits synergy with pDC activators, such as microbial cytosine- phosphate- guanosine (CpG) DNA. CONCLUSIONS:
GM-CSF is effective in the treatment of DSS colitis in a mechanism involving the 440c(+) pDC population.
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Authors | Satheesh K Sainathan, Eyad M Hanna, Qingqing Gong, Kumar S Bishnupuri, Qizhi Luo, Marco Colonna, Frances V White, Ed Croze, Courtney Houchen, Shrikant Anant, Brian K Dieckgraefe |
Journal | Inflammatory bowel diseases
(Inflamm Bowel Dis)
Vol. 14
Issue 1
Pg. 88-99
(Jan 2008)
ISSN: 1078-0998 [Print] England |
PMID | 17932977
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Homeodomain Proteins
- Interferon Type I
- Interleukin-1beta
- Recombinant Proteins
- Tumor Necrosis Factor-alpha
- RAG-1 protein
- sargramostim
- Granulocyte-Macrophage Colony-Stimulating Factor
- Dextran Sulfate
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Topics |
- Animals
- Colitis
(chemically induced, immunology, pathology, physiopathology)
- Colon
(pathology)
- Dendritic Cells
(immunology)
- Dextran Sulfate
(toxicity)
- Female
- Granulocyte-Macrophage Colony-Stimulating Factor
(immunology)
- Homeodomain Proteins
(genetics)
- Interferon Type I
(immunology)
- Interleukin-1beta
(genetics)
- Intestinal Mucosa
(pathology)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Oligonucleotide Array Sequence Analysis
- Recombinant Proteins
- Tumor Necrosis Factor-alpha
(genetics)
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