Characterization of the kynurenine pathway in human oligodendrocytes

Abstract

It is important to understand the involvement of oligodendrocytes in the kynurenine pathway (KP) and more particularly, their potential ability to produce neuroprotective metabolites such as kynurenic acid (KYNA) or picolinic acid (PIC), and the possibility of taking up and catabolizing the excitotoxin quinolinic acid (QUIN). These mechanisms may play a crucial role in the pathophysiology of neuroinflammatory diseases, especially multiple sclerosis. We used RT-PCR and HPLC to delineate KP enzyme expression and KP metabolite production. We characterized the KP in oligodendrocytes and showed that they lack IDO expression and are unable to catabolize tryptophan. However, the other enzymes in the pathway are present. These results indicate that human oligodendrocytes are more likely to produce neuroprotective KP metabolites such as KYNA and PIC rather than QUIN. However, because of the lack of IDO they are not able to down-regulate the immune response and as such may be more vulnerable to autoimmune phenomena.