Quinolinic acid up-regulates 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 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-alpha/IFN-gamma. 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-1alpha (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-alpha/IFN-gamma. 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.
Croitoru-Lamoury
Juliana
J
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
Guillemin
Gilles J
GJ
Dormont
D
D
Brew
Bruce J
BJ
D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D017378:Quinolinic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D017378:Quinolinic Acid