Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.
Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood ce...
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oai:doaj.org-article:2238c69f5a2048f0baf5983c496fdbc72021-11-18T06:53:57ZPlatelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.1932-620310.1371/journal.pone.0019651https://doaj.org/article/2238c69f5a2048f0baf5983c496fdbc72011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21603600/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.Mathieu BarbierDorothée FailleBéatrice LoriodJulien TextorisClaire CamusDenis PuthierLaurence FloriSamuel Crocodile WassmerGeneviève VictoreroMarie-Christine AlessiThierry FusaïCatherine NguyenGeorges E GrauPascal RihetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19651 (2011) |
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Medicine R Science Q Mathieu Barbier Dorothée Faille Béatrice Loriod Julien Textoris Claire Camus Denis Puthier Laurence Flori Samuel Crocodile Wassmer Geneviève Victorero Marie-Christine Alessi Thierry Fusaï Catherine Nguyen Georges E Grau Pascal Rihet Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| description |
Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM. |
| format |
article |
| author |
Mathieu Barbier Dorothée Faille Béatrice Loriod Julien Textoris Claire Camus Denis Puthier Laurence Flori Samuel Crocodile Wassmer Geneviève Victorero Marie-Christine Alessi Thierry Fusaï Catherine Nguyen Georges E Grau Pascal Rihet |
| author_facet |
Mathieu Barbier Dorothée Faille Béatrice Loriod Julien Textoris Claire Camus Denis Puthier Laurence Flori Samuel Crocodile Wassmer Geneviève Victorero Marie-Christine Alessi Thierry Fusaï Catherine Nguyen Georges E Grau Pascal Rihet |
| author_sort |
Mathieu Barbier |
| title |
Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| title_short |
Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| title_full |
Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| title_fullStr |
Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| title_full_unstemmed |
Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| title_sort |
platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/2238c69f5a2048f0baf5983c496fdbc7 |
| work_keys_str_mv |
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