人单核细胞衍生巨噬细胞合成与释放神经毒性犬尿氨酸代谢产物。

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

作者信息

Chiarugi A, Calvani M, Meli E, Traggiai E, Moroni F

机构信息

Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.

出版信息

J Neuroimmunol. 2001 Nov 1;120(1-2):190-8. doi: 10.1016/s0165-5728(01)00418-0.

DOI:10.1016/s0165-5728(01)00418-0

PMID:11694334

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 INFgamma and TNFalpha increased, while IL 4 or IL 10 inhibited the rate of tryptophan metabolism and the release of QUIN. The incubation media of INFgamma-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.

摘要

我们研究了人单核细胞衍生巨噬细胞（MDM）中色氨酸代谢的犬尿氨酸途径的调节，目的是评估巨噬细胞在炎症性神经疾病中的作用。培养的MDM代谢色氨酸并释放犬尿氨酸代谢产物，包括兴奋性毒素喹啉酸（QUIN）。脂多糖（LPS）或促炎细胞因子INFγ和TNFα可增加色氨酸代谢率和QUIN的释放，而IL-4或IL-10则抑制其释放。暴露于INFγ的MDM的培养液可导致混合皮质细胞原代培养物中的神经元死亡。谷氨酸受体拮抗剂或聚（ADP-核糖）聚合酶抑制剂可显著减少这种死亡，从而为神经炎症性疾病中神经元损伤的治疗提供了新的可能性。