Quinolinic Acid Up-Regulates Chemokine Production and Chemokine Receptor Expression in Astrocytes

  • Juliana Croitoru-Lamoury
  • Gilles J. Guillemin
  • D. Dormont
  • Bruce J. Brew
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 527)

Abstract

Within the brain, quinolinic acid (QUIN) is an important neurotoxin, especially in AIDS dementia complex (ADC). Its production by monocytic lineage cells is increased in the context of inflammation. However, it is not known whether QUIN promotes inflammation. Astrocytes are important in immuno-regulation within the brain and so we chose to examine the effects of QUIN on the astrocyte. Using purified cultures of primary human foetal astrocyte, we determined chemokine production using ELISA assays and RT-PCR, and chemokine receptor expression using immunocytochemistry and RT-PCR with QUIN in comparison to TNF-a/IFN-y. We found that QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-la (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3 in human foetal astrocytes. Most of these effects were comparable to those induced by TNF-a/IFN-y. The present work represents the first evidence that QUIN induces chemokine and chemokine receptor expression in astrocytes and is at least as potent as classical mediators such as inflammatory cytokines. These results suggest that QUIN may be critical in the amplification of brain inflammation particularly in ADC.

Keywords

Human Immunodeficiency Virus Type Chemokine Receptor Quinolinic Acid Human Astrocyte Kynurenine Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Juliana Croitoru-Lamoury
    • 1
  • Gilles J. Guillemin
    • 2
  • D. Dormont
    • 3
  • Bruce J. Brew
    • 4
  1. 1.Commissariat a l’Energie Atomique,Department of NeurovirologyFontenay-aux-RosesFrance
  2. 2.Centre for Immunology,Departments of Neurology and HIV MedicineSt Vincent’s HospitalSydneyAustralia
  3. 3.Commissariat a l’Energie Atomique,Department of NeurovirologyFontenay-aux-RosesFrance
  4. 4.Departments of Neurology and HIV MedicineSt Vincent’s HospitalSydneyAustralia

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