HIV-1 tat protein upregulates inflammatory mediators and induces monocyte invasion into the brain

Hong Pu, Jing Tian, Govinder Flora, Yong Woo Lee, Avindra Nath, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

Abstract

Impaired inflammatory functions may be critical factors in the mechanisms by which HIV-1 enters the CNS. Evidence indicates that a viral gene product, the protein Tat, can markedly contribute to these effects. In the present study we tested the hypothesis that Tat can upregulate the expression of inflammatory cytokines and adhesion molecules and facilitate the entry of monocytes into the brain. Expression of inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was assessed in C57BL/6 mice injected with Tat1-72 into the right hippocampus. In the Tat1-72-injected groups, mRNA and protein levels of MCP-1, TNF-α, VCAM-1, and ICAM-1 were markedly elevated compared to those in control animals. The most pronounced changes were observed in and around the injected hippocampus. Double-labeling immunohistochemistry demonstrated that inflammatory proteins were primarily expressed in activated microglial cells and perivascular cells. In addition, astrocytes and endothelial cells were susceptible to Tat1-72-induced inflammatory responses. These changes were associated with a substantial infiltration of monocytes into the brain. These data demonstrate that intracerebral administration of Tat can induce profound proinflammatory effects in the brain, leading to monocyte infiltration.

Original languageEnglish (US)
Pages (from-to)224-237
Number of pages14
JournalMolecular and Cellular Neuroscience
Volume24
Issue number1
DOIs
StatePublished - Sep 1 2003

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Keywords

  • Blood-brain barrier
  • Brain endothelium
  • HIV
  • Inflammatory responses
  • NeuroAIDS

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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