Progesterone alters kynurenine pathway activation in IFN-γ-activated macrophages - relevance for neuroinflammatory diseases

J. de Bie, C. K. Lim, G. J. Guillemin*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferon-gamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation.

    Original languageEnglish
    Pages (from-to)89-93
    Number of pages5
    JournalInternational Journal of Tryptophan Research
    Volume9
    DOIs
    Publication statusPublished - 2016

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