Expression of the kynurenine pathway enzymes in human microglia and macrophages

Gilles J. Guillemin*, Danielle G. Smith, George A. Smythe, Patricia J. Armati, Bruce J. Brew

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)

Abstract

There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN) play a role in the pathogenesis of neurological diseases. Monocytic cells are known to be the major producers of QUIN. However, macrophages have the ability to produce approximately 20 to 30-fold more QUIN than microglia. The molecular origin of this difference has not been clarified yet. Using unstimulated and IFN-γ-stimulated cultures of human fœtal microglia and adult macrophages, we assayed mRNA expression of 8 key enzymes of the KP using RT-PCR and QUIN production using GC-MS. We found that after stimulation with IFN-γ microglia produced de novo 20-fold less QUIN than macrophages. This quantitative difference in the ability to produce QUIN appears to be associated with a lower expression of 3 important enzymes of the KP in microglia: indoleamine 2,3-dioxygenase (IDO), kynureninase (KYNase) and kynurenine hydroxylase (KYN(OH)ase). These results suggest that activated infiltrating macrophages are the most potent QUIN producers during brain inflammatory diseases with playing a lesser role.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Volume527
Publication statusPublished - 2003
Externally publishedYes

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