Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes.
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 immunoregulation within the brain and so we chose to examine the effects of QUIN on the astrocyte. Using purified primary human fetal astrocyte cultures, we determined chemokine production using ELISA assays and RT-PCR and chemokine receptor expression using immunocytochemistry and RT-PCR with QUIN in comparison to TNFalpha, IL-1beta, and IFNgamma. We found that QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2) and lesser amounts of RANTES (CCL5) and IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9), and fractalkine (CX(3)CL1) mRNA expression. Moreover, QUIN leads to upregulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3 in human fetal astrocytes. Most of these effects were comparable to those induced by TNFalpha, IL-1beta, and IFNgamma. 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.
Guillemin
Gilles J
GJ
Centre for Immunology, St Vincent's Hospital, Sydney, Australia. g.guillemin@cfi.unsw.edu.au
Croitoru-Lamoury
Juliana
J
Dormont
Dominique
D
Armati
Patricia J
PJ
Brew
Bruce J
BJ
D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017378:Quinolinic Acid / Q000494:pharmacology*; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D018925:Chemokines; D019707:Receptors, Chemokine; D017378:Quinolinic Acid