Synthesis and release of neurotoxic kynurenine metabolites by human monocyte-derived macrophages

被引:96
作者
Chiarugi, A
Calvani, M
Meli, E
Traggiai, E
Moroni, F
机构
[1] Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy
[2] Univ Florence, Dept Neurol & Psychiat, I-50139 Florence, Italy
关键词
quinolinic acid; 30H-kynurenine; cytokines; excitotoxicity; interferon gamma; LPS;
D O I
10.1016/S0165-5728(01)00418-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 NDM metabolized tryptophan and released kynurenine metabolites, including the excitotoxin quinolinic acid (QUIN). Lipopolysaccharides (LPS) or the pro-inflammatory cytokines INIF gamma and TNF alpha increased, while IL 4 or IL 10 inhibited the rate of tryptophan metabolism and the release of QUIN. The incubation media of INF gamma -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. (C) 2001 Published by Elsevier Science B.V.
引用
收藏
页码:190 / 198
页数:9
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