Quinolinic Acid Is Produced by Macrophages Stimulated by Platelet Activating Factor, Nef and Tat

J Neurovirol. 2001 Feb;7(1):56-60. doi: 10.1080/135502801300069692.

Abstract

Activated macrophages produce quinolinic acid (QUIN), a neurotoxin, in several inflammatory brain diseases including AIDS dementia complex. We hypothesized that IL1-beta, IL6, transforming growth factor (TGF-beta2 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-beta, IL6, TGF-beta2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / etiology
  • AIDS Dementia Complex / metabolism
  • Enzyme Induction / drug effects
  • Gene Products, nef / pharmacology*
  • Gene Products, tat / pharmacology*
  • HIV Envelope Protein gp41 / pharmacology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology
  • Macrophages / chemistry
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Platelet Activating Factor / pharmacology*
  • Quinolinic Acid / analysis
  • Quinolinic Acid / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta2
  • Tryptophan Oxygenase / metabolism
  • nef Gene Products, Human Immunodeficiency Virus
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, nef
  • Gene Products, tat
  • HIV Envelope Protein gp41
  • Interleukin-1
  • Interleukin-6
  • Platelet Activating Factor
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • nef Gene Products, Human Immunodeficiency Virus
  • tat Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma
  • Tryptophan Oxygenase
  • Quinolinic Acid