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Synthesis and release of neurotoxic kynurenine metabolites by human monocyte-derived macrophages |
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| Authors: | Alberto Chiarugi Maura Calvani Elena Meli Elisabetta Traggiai Flavio Moroni |
| Affiliation: | a Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy b Department of Neurology and Psychiatry, University of Florence, 50139 Florence, Italy |
| Abstract: | We studied the regulation of the kynurenine pathway of tryptophan metabolism in human monocyte-derived macrophages (MDM) with the aim of evaluating macrophage involvement in inflammatory neurological disorders. Cultured MDM metabolized tryptophan and released kynurenine metabolites, including the excitotoxin quinolinic acid (QUIN). Lipopolysaccharides (LPS) or the pro-inflammatory cytokines INFγ and TNF increased, while IL 4 or IL 10 inhibited the rate of tryptophan metabolism and the release of QUIN. The incubation media of INFγ-exposed MDM caused neuronal death in primary cultures of mixed cortical cells. Glutamate receptor antagonists or poly(ADP-ribose) polymerase inhibitors significantly reduced this death, thus suggesting new possibilities for the treatment of neuronal damage in neuroinflammatory disorders. |
| Keywords: | Quinolinic acid 3OH-kynurenine Cytokines Excitotoxicity Interferon γ LPS |
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