Proinflammatory synergism of ethanol and HIV-1 Tat protein in brain tissue

Govinder Flora, Hong Pu, Yong Woo Lee, R. Ravikumar, Avindra Nath, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat protein is a potent transactivator of viral replication. It is actively released from HIV-infected cells and has been shown to induce cell injury effects. Alcohol abuse is a risk factor of HIV infection and we hypothesize that alcohol and Tat may interact in an additive or synergistic fashion to influence molecular processes which can contribute to their toxic effects. To study this possibility, we investigated the effects of two intraperitoneal injections of ethanol (EtOH, 3 g/kg each, 16 h apart) and a single intracerebral injection of Tat (25 μg/μl into the right hippocampus, injected 12 h after the first EtOH injection) on generation of cellular oxidative stress, DNA binding activity of redox-responsive transcription factors, and induction of inflammatory genes in the hippocampus and corpus striatum of mouse brain. As compared to control animals, treatment with EtOH plus Tat resulted in increased production of reactive oxygen species in both brain regions. In addition, DNA binding activities of nuclear factor-κB (NF-κB) and CREB in both brain regions and SP-1 in the hippocampus were more pronounced in mice injected with Tat plus EtOH as compared to the effects of Tat or EtOH alone. Among studied inflammatory genes, induction of IL-1β and MCP-1 was potentiated in animals injected with EtOH plus Tat. These results indicate that Tat and EtOH can cross-amplify their cellular effects, leading to alterations of redox-regulated inflammatory pathways in the brain. Such potentiation of proinflammatory stimulation may further contribute to CNS pathology in HIV-infected patients who are alcohol abusers.

Original languageEnglish
Pages (from-to)2-12
Number of pages11
JournalExperimental Neurology
Volume191
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

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Keywords

  • Adhesion molecules
  • Brain regions
  • Cytokines
  • Ethanol
  • HIV-1
  • Oxidative stress
  • Tat
  • Transcription factors

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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