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| Status |
Public on Apr 09, 2009 |
| Title |
Hydroxyurea stimulates production of pro-inflammatory cytokines in endothelial cells: Relevance to sickle cell disease. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In sickle cell disease (SCD) hemoglobin S (HbS) polymerization renders red blood cells (RBC) both fragile and rigid and accounts for anemia and vasoocclusive crises (VOC). Abnormal RBC adhesion to vascular endothelial cells (VEC), in a context of chronic inflammation, cell activation and vascular tone abnormalities, is a major event in triggering VOC. Hydroxyurea (HU) is the only drug with a proven efficiency at decreasing VOC occurrence. HU decreases HbS polymerization and RBC adhesion. We studied HU effect on the other cellular partner of adhesion, i.e.VEC. HU-induced TrHBMEC transcriptome variations were analyzed by micro-arrays both in basal and pro-inflammatory conditions after 24h and 48h of treatment. Among the endothelial HU target genes we focused on those related to adhesion and inflammation phenomena. HU had no impact on adhesion genes as a whole, still expression of VCAM-1, a key adhesion receptor, was decreased. In contrast, HU had a significant effect on the inflammation gene cluster. It stimulates pro-inflammatory genes such as IL-1A, IL-1B, IL-6, IL-8, CCL2, CCL5 and CCL8 both at the mRNA and protein levels and also in HPMEC and HUVEC primary cells. This may suggest that HU increases inflammation in SCD patients to a threshold engaging an anti-inflammatory response.
Keywords: Treated TrHBME cell line
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| Overall design |
Biological and technical relicates, 4 conditions: TrHBME cells non-treated, treated with cytokine, hydroxyurea or both and observed after 24 or 48H
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| Contributor(s) |
Laurance S, Benecke A, Dossou-Yovo OP, Pellay F, Hauchecorne M, Verger E, Lapoumeroulie C, Elion J |
| Citation(s) |
21228039 |
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| Submission date |
May 07, 2008 |
| Last update date |
Jan 27, 2016 |
| Contact name |
Arndt Benecke |
| E-mail(s) |
arndt@ihes.fr
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| Phone |
+33160926665
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| Fax |
+33160926609
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| URL |
http://seg.ihes.fr
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| Organization name |
Institut des Hautes Etudes Scientifiques & I.R.I.-CNRS
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| Department |
Integrative Biology
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| Lab |
Systems Epigenomics
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| Street address |
35 route des Chartres
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| City |
Bures-sur-Yvette |
| ZIP/Postal code |
91440 |
| Country |
France |
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| Platforms (2) |
| GPL1426 |
ABI Human Genome Survey Microarray Version 1 |
| GPL2986 |
ABI Human Genome Survey Microarray Version 2 |
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| Samples (45)
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| Relations |
| BioProject |
PRJNA106597 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11372_RAW.tar |
16.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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