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| Status |
Public on Nov 10, 2009 |
| Title |
Effect of Plasmodium falciparum infected erythrocytes on primary human brain microvascular endothelial cell |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparum–infected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparum–modulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparum–infected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
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| Overall design |
Total of 8 samples (4 control and 4 treated) were analyzed. 4 control samples included two normal RBC control and two medium controls. 4 treated samples includes 2 exposed to low binding Pf-IRBC and 2 exposed to high binding Pf-IRBC (Pf-IRBC-P). Medium and RBC controls were finally used as four replicates of control and all four Pf-IRBC or Pf-IRBC-P exposed endothelial cells were used as 4 separate treated controls.
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| Contributor(s) |
Tripathi AK, Stins MF, Sha W, Shulaev V, Sullivan DJ |
| Citation(s) |
19713460 |
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| Submission date |
Dec 12, 2007 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Abhai K Tripathi |
| E-mail(s) |
atripath@jhsph.edu, mstins@jhmi.edu, dsulliva@jhsph.edu
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| Phone |
410-614-1562
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| Fax |
410-955-0105
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| Organization name |
Johns Hopkins University
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| Department |
Mol Microbiol and Immunology, SPH and Neurology, SOM
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| Lab |
Sullivan, DJ (MMI) and Stins MF (Neurology)
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| Street address |
615 N Wolfe St
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA103845 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9861_RAW.tar |
14.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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