Quinolinic acid is produced by macrophages stimulated platelet activating factor, Nef and Tat

D. G. Smith, G. J. Guillemin, L. Pemberton, S. Kerr, A. Nath, G. A. Smythe, B. J. Brew

Research output: Contribution to journalArticlepeer-review

Abstract

Activated macrophages produce quinolinic acid (QUIN), a neurotoxin, in several inflammatory brain diseases including AIDS dementia complex. We hypothesized that IL1-β, IL6, transforming growth factor (TGF-β2) and platelet activating factor could increase macrophage QUIN production. And that the HIV-1 proteins Nef, Tat and gp41 may also increase synthesis of QUIN by macrophages. At 72 h there were significant increases in QUIN production in the cells stimulated with PAF (914 ± 50 nM) and Nef (2781 ± 162 nM), with somewhat less production by Tat stimulation (645 ± 240 nM). The increases in QUIN production approximated in vitro concentrations of QUIN shown to be neurotoxic and correlated closely with indoleamine 2,3-dioxygenase induction. IL1-β, IL6, TGF-β2 and gp41 stimulation produced no significant increase in QUIN production. These results suggest that some of the neurotoxicity of PAF, nef and tat may be mediated by QUIN.

Original languageEnglish (US)
Pages (from-to)56-60
Number of pages5
JournalJournal of neurovirology
Volume7
Issue number1
DOIs
StatePublished - Oct 9 2001

Keywords

  • ACD
  • HIV-1
  • Kynurenine pathway

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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