Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes: A hit and run phenomenon

Avindra Nath, Katherine Conant, Peiqin Chen, Catherine Scott, Eugene O. Major

Research output: Contribution to journalArticlepeer-review

Abstract

The pathological correlates of dementia due to human immunodeficiency virus (HIV) infection are glial cell activation and cytokine dysregulation. These findings occur in the setting of small numbers of productively infected cells within the brain. We determined whether exposure of susceptible cells to Tat protein of HIV could result in the production of select proinflammatory cytokines. In a dose-responsive manner, Tat induced interleukin (IL)-1β production in monocytic cells, while astrocytic cells showed an increase in mRNA for IL-1β, but had a translation block for IL- 1β protein production. Conversely, IL-6 protein and mRNA productions were strongly induced in astrocytic cells and minimally in monocytic cells. IL- 1β and IL-6 production were independent of tumor necrosis factor-α production. All exposure to Tat for a few minutes was sufficient for sustained releases of cytokines for several hours. This prolonged cytokine production is likely maintained by a positive feed back loop of Tat-induced nuclear factor κB activation and cytokine production that is independent of extracellular calcium. Thus a transient exposure may be sufficient to initiate a cascade of events resulting in cerebral dysfunction and a 'hit and run' approach may be in effect. Hence cross-sectional measurement of viral load in the brain may not be a useful indicator of the role of viral products in the neuropathogenesis of HIV dementia.

Original languageEnglish (US)
Pages (from-to)17098-17102
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number24
DOIs
StatePublished - Jun 11 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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