title: Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.
abstract: 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.
authors: Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France.
authors: Mathieu
authors: M
authors: Barbier
authors: Dorothée
authors: D
authors: Faille
authors: Béatrice
authors: B
authors: Loriod
authors: Julien
authors: J
authors: Textoris
authors: Claire
authors: C
authors: Camus
authors: Denis
authors: D
authors: Puthier
authors: Laurence
authors: L
authors: Flori
authors: Samuel Crocodile
authors: SC
authors: Wassmer
authors: Geneviève
authors: G
authors: Victorero
authors: Marie-Christine
authors: MC
authors: Alessi
authors: Thierry
authors: T
authors: Fusaï
authors: Catherine
authors: C
authors: Nguyen
authors: Georges E
authors: GE
authors: Grau
authors: Pascal
authors: P
authors: Rihet
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