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| Status |
Public on Nov 12, 2011 |
| Title |
The immunoregulatory effect of macrophage-specific PPAR gamma deficiency on experimental inflammatory bowel disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Inflammatory bowel disease (IBD) is a condition characterized by severe intestinal inflammation and immune cell activation. The severity of the disease can be mitigated by compounds which activate peroxisome proliferator-activated receptor gamma (PPAR gamma), a receptor present widely in tissues involved in IBD pathogenesis. Our objective was to assess the affect of macrophage-specific deficiency of PPAR gamma on peripheral and colonic immune populations and colonic gene expression in experimental IBD. Macrophage-specific PPAR gamma-deficient mice (PPAR gamma flfl Lysozyme M Cre+) and control (PPAR gamma flfl Lysozyme M Cre-) littermates were treated with 2.5% dextran sodium sulfate (DSS) for 7 days. Disease activity was recorded daily and immune cell populations in the blood, spleen, mesenteric lymph nodes (MLN), and lamina propria were examined by flow cytometry. Colonic gene expression was assessed by real time PCR and microarray analyses. Our findings show that macrophage PPAR r-deficiency significantly exacerbates DSS inflammation. CD4+CD25+FoxP3+ regulatory T cells (T-regs) were significantly reduced in Cre+ mice, and MLN macrophages and CD40 expression were enhanced. There were significant differences in the number colonic macrophages between Cre+ and Cre- mice, but those from Cre+ mice expressed more CD40, Ly6C, and TLR-4. PPAR r-deficiency also increased the percent of CD8+ T cells in the lamina propria and enhanced colonic interferon gamma expression. Our findings indicate that macrophage PPAR gamma deficiency augments the severity of DSS colitis by reducing peripheral T-regs and increasing colonic macrophage activation and T cell inflammation.
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| Overall design |
RNA from 3 PPAR gamma-deficient mice (PPAR gamma flfl; Lysozyme M Cre+) and 3 control (PPAR gamma flfl; Lysozyme M Cre-) littermates was processed and labeled according to the standard target labeling protocols. The samples were hybridized, stained, and scanned per standard Affymetrix protocols at the Virginia Bioinformatics Institute (VBI) core laboratory on Mouse 430 2.0 expression arrays (Affymetrix Inc., Santa Clara, CA).
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| Contributor(s) |
Hontecillas R, Horne WT, Guri AJ, Zhang Y, Sobral B, Bassaganya-Riera J |
| Citation(s) |
21068720 |
| Submission date |
Aug 04, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Maria Salvato |
| E-mail(s) |
MSalvato@ihv.umaryland.edu
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| Phone |
410-706-1368
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| Organization name |
University of Maryland School of Medicine
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| Department |
Institute of Human Virology
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| Lab |
Rm 510
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| Street address |
725 W Lombard Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21201 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM574340 |
colonic tissue from floxed mouse, biological rep1 |
| GSM574341 |
colonic tissue from floxed mouse, biological rep2 |
| GSM574342 |
colonic tissue from floxed mouse, biological rep3 |
| GSM574343 |
colonic tissue from macrophage-specific PPARgamma-deficient mouse, biological rep1 |
| GSM574344 |
colonic tissue from macrophage-specific PPARgamma-deficient mouse, biological rep2 |
| GSM574345 |
colonic tissue from macrophage-specific PPARgamma-deficient mouse, biological rep3 |
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| Relations |
| BioProject |
PRJNA131037 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23421_RAW.tar |
20.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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