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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4243-4252. Prepublished online as a Blood First Edition Paper on August 27, 2009; DOI 10.1182/blood-2009-06-226415. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-06-226415v1 114/19/4243    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Tripathi, A. K. Articles by Sullivan, D. J. PubMed PubMed Citation Articles by Tripathi, A. K. Articles by Sullivan, D. J., Jr Related Collections Red Cells, Iron, and Erythropoiesis Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS Plasmodium falciparum–infected erythrocytes induce NF-B regulated inflammatory pathways in human cerebral endothelium Abhai K. Tripathi1, Wei Sha2, Vladimir Shulaev2, Monique F. Stins3, and David J. Sullivan, Jr1 1 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; 2 Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg; and 3 Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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