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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 02, 2009 |
| Title |
Immunomodulatory effect of 5-azacytidine (5-azaC): potential role in the transplantation setting. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cytokine genes are targets of multiple epigenetic mechanisms in T lymphocytes. 5-azacytidine (5-azaC) is a nucleoside-based DNA methyltransferases (DNMT) inhibitor which induces demethylation and gene reactivation. In the current study, we analyzed the effect of 5-azaC in T-cell function and observed that 5-azaC inhibits T-cell proliferation and activation, blocking cell cycle in G0-G1 phase and decreasing the production of proinflammatory cytokines such as TNFα and IFNγ. This effect was not due to a pro-apoptotic effect of the drug but to the down-regulation of genes involved in T-cell cycle progression and activation such as CCNG2, MTCP1, CD58, and ADK and up-regulation of genes which induce cell growth arrest, such as DCUN1D2, U2AF2, GADD45B or p53. In spite of being also up-regulated, we did not find any effect of 5-azaC on the methylation pattern of FOXP3. Finally, the administration of 5-azaC at 60 and 84 hours post-transplant prevented the development of GVHD leading to a significant increase in survival in a fully mismatched BMT mouse model. In conclusion, the current study shows the effect of 5-azaC in T-lymphocytes and illustrates its role in the allogeneic transplantation setting as an immunomodulatory drug, describing new pathways which must be explored in order to prevent graft-versus-host disease.
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| Overall design |
In order to elucidate the mechanisms involved in the effect of 5-azaC on T-cells we performed Affymetrix gene expression assays in T-cells untreated versus treated with 5-azaC at 1 μM after 2 and 4 days of culture, making a total of 12 samples (coming from time-series studies of 3 healthy individuals)
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| Contributor(s) |
Sánchez-Abarca LI, Gutierrez-Cosio S, Santamaría C, Caballero-Velazquez T, Blanco B, Herrero-Sánchez C, Garcia JL, González FJ, Carrancio S, Hernández-Campo P, Flores T, Del-Cañizo C, San-Miguel JF, Pérez-Simón JA |
| Citation(s) |
19887673 |
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| Submission date |
Sep 01, 2009 |
| Last update date |
Jul 26, 2018 |
| Contact name |
José Antonio Pérez Simón |
| E-mail(s) |
pesimo@usal.es
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| Phone |
+34923291384
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| URL |
http://www.cicancer.org
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| Organization name |
University Hospital
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| Department |
Hematology Service
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| Lab |
Cellular Therapy
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| Street address |
Paseo de San Vicente, s/n
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| City |
Salamanca |
| State/province |
Salamanca |
| ZIP/Postal code |
E-37007 |
| Country |
Spain |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| GSM447769 |
Control T cells at T4, biological replicate 1 |
| GSM447770 |
Treated T cells at T4, biological replicate 1 |
| GSM447771 |
Control T cells at T0, biological replicate 2 |
| GSM447772 |
Control T cells at T2, biological replicate 2 |
| GSM447773 |
Treated T cells at T2, biological replicate 2 |
| GSM447774 |
Control T cells at T4, biological replicate 2 |
| GSM447775 |
Treated T cells at T4, biological replicate 2 |
| GSM447776 |
Control T cells at T0, biological replicate 3 |
| GSM447777 |
Control T cells at T2, biological replicate 3 |
| GSM447778 |
Treated T cells at T2, biological replicate 3 |
| GSM447779 |
Control T cells at T4, biological replicate 3 |
| GSM447780 |
Treated T cells at T4, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA119883 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17922_AnnotatedNormalizedDataMatrix.xls.gz |
15.0 Mb |
(ftp)(http) |
XLS |
| GSE17922_RAW.tar |
55.5 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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