HIV-1 activates proinflammatory and interferon-inducible genes in human brain microvascular endothelial cells: Putative mechanisms of blood-brain barrier dysfunction

Anathbandhu Chaudhuri, Fenghai Duan, Brenda Morsey, Yuri Persidsky, Georgette D. Kanmogne

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The mechanisms underlying blood-brain barrier (BBB) dysfunction seen in human immunodeficiency virus 1 (HIV-1) infection are poorly understood; however, they are believed to be caused by interactions of human brain microvascular endothelial cells (HBMEC) with virus-infected macrophages. Using a transwell system and Affymetrix arrays, we investigated HIV-1-induced genomic changes in HBMEC after coculture with HIV-1-infected or -uninfected monocyte-derived macrophages (MDM). Differentially expressed genes were determined by linear modeling and then were grouped by hierarchical clustering. Compared to HBMEC cocultured with noninfected MDM, 184 probe sets corresponding to 84 genes were differentially expressed in HBMEC cocultured with HIV-infected MDM. Genes activated in HIV-1 MDM-exposed HBMEC included proinflammatory cytokines and chemokines, tumor necrosis factor-α-induced proteins, interferon (IFN)-inducible genes, intercellular adhesion molecule-1, transcription factors of the nuclear factor-κB family, and signal transducer and activator of transcription 1. Analysis of molecular networks and canonical pathways associated with differentially expressed genes suggest that HIV-1 causes BBB impairment by mechanisms involving inflammation, cytokine, and IFN signaling in HBMEC.

Original languageEnglish (US)
Pages (from-to)697-711
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Blood-brain barrier
  • Cell signaling
  • HIV-1
  • Inflammation
  • Injury
  • Monocyte-derived macrophages

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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